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<!-- DFIN ActiveDisclosure(SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-08-13T14:16:51.5464470+00:00 -->
<!-- Version            : 5.0.1.476 -->
<!-- Package ID         : 036c626a70da4f6ca467e921b34e9487 -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="rptx_SeriesAConvertiblePreferredSharesMember" name="SeriesAConvertiblePreferredSharesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_SeriesBConvertiblePreferredSharesMember" name="SeriesBConvertiblePreferredSharesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_TemporaryEquitySharesAuthorizedUnlimited" name="TemporaryEquitySharesAuthorizedUnlimited" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_PreferredStockAuthorizedUnlimited" name="PreferredStockAuthorizedUnlimited" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_ChangeInFairValueOfPreferredShareTrancheObligation" name="ChangeInFairValueOfPreferredShareTrancheObligation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_NetIncomeLossAndComprehensiveIncomeLoss" name="NetIncomeLossAndComprehensiveIncomeLoss" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" name="TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_IssuanceOfWarrantsAndConversionIntoCommonStockDuringPeriodShares" name="IssuanceOfWarrantsAndConversionIntoCommonStockDuringPeriodShares" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_IssuanceOfWarrantsAndConversionIntoCommonStockDuringPeriodValue" name="IssuanceOfWarrantsAndConversionIntoCommonStockDuringPeriodValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_ForeignCurrencyTransactionGainLoss" name="ForeignCurrencyTransactionGainLoss" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_IncreaseDecreaseInResearchAndDevelopmentTaxCreditsReceivable" name="IncreaseDecreaseInResearchAndDevelopmentTaxCreditsReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_IncreaseDecreaseInAccruedExpensesAndOtherCurrentLiabilities" name="IncreaseDecreaseInAccruedExpensesAndOtherCurrentLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_IncreaseDecreaseInOperatingLeaseLiabilityCurrent" name="IncreaseDecreaseInOperatingLeaseLiabilityCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_IncreaseDecreaseInOperatingLeaseLiabilityNet" name="IncreaseDecreaseInOperatingLeaseLiabilityNet" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_PropertyAndEquipmentPurchasesInAccountsPayable" name="PropertyAndEquipmentPurchasesInAccountsPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_InitialPublicOfferingCostsInAccountsPayable" name="InitialPublicOfferingCostsInAccountsPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_InitialPublicOfferingCostsInAccrualsAndOtherCurrentLiabilities" name="InitialPublicOfferingCostsInAccrualsAndOtherCurrentLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_SignificantAgreementsAndCommitmentsTextBlock" name="SignificantAgreementsAndCommitmentsTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_SignificantAgreementsAndCommitmentsDisclosureAbstract" name="SignificantAgreementsAndCommitmentsDisclosureAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_COVID19PandemicPolicyTextBlock" name="COVID19PandemicPolicyTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" name="ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_SummaryOfOtherOperatingLeaseInformationTableTextBlock" name="SummaryOfOtherOperatingLeaseInformationTableTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_OrganizationAndNatureOfBusinessLineItems" name="OrganizationAndNatureOfBusinessLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_OrganizationAndNatureOfBusinessTable" name="OrganizationAndNatureOfBusinessTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_GrossProceedsFromInitialPublicOffering" name="GrossProceedsFromInitialPublicOffering" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_AccruedResearchAndDevelopmentExpenseCurrent" name="AccruedResearchAndDevelopmentExpenseCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_AccruedInitialPublicOfferingCosts" name="AccruedInitialPublicOfferingCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_AccruedExpensesAndOtherLiabilitiesCurrent" name="AccruedExpensesAndOtherLiabilitiesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_BristolMyersSquibbCompanyMember" name="BristolMyersSquibbCompanyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_ResearchDevelopmentAndRegulatoryMilestonesMember" name="ResearchDevelopmentAndRegulatoryMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_CommercialMilestonesMember" name="CommercialMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_CollaborationAndLicenseAgreementMember" name="CollaborationAndLicenseAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_DeferredRevenueMember" name="DeferredRevenueMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_AffiliateOfBristolMyersSquibbCompanyMember" name="AffiliateOfBristolMyersSquibbCompanyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_NumberOfOperatingLeases" name="NumberOfOperatingLeases" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_TwoThousandTwentyEmployeeSharePurchasePlanMember" name="TwoThousandTwentyEmployeeSharePurchasePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_RepareTherapeuticsIncorporationOptionPlanMember" name="RepareTherapeuticsIncorporationOptionPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_TwoThousandTwentyEquityIncentivePlanMember" name="TwoThousandTwentyEquityIncentivePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_AnnualIncreaseInNumberOfSharesAvailableForIssuanceAsPercentageOnOutstandingSharesOfCommonStockOnFinalDayOfPrecedingCalendarYear" name="AnnualIncreaseInNumberOfSharesAvailableForIssuanceAsPercentageOnOutstandingSharesOfCommonStockOnFinalDayOfPrecedingCalendarYear" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_PurchasePriceOfSharesAsPercentageOfFairMarketValueOfCommonStockOnDateOfPurchase" name="PurchasePriceOfSharesAsPercentageOfFairMarketValueOfCommonStockOnDateOfPurchase" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_AnnualIncreaseInNumberOfSharesAvailableForIssuanceMaximumNumberOfCommonStockIssued" name="AnnualIncreaseInNumberOfSharesAvailableForIssuanceMaximumNumberOfCommonStockIssued" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_CommonStockCapitalSharesInitiallyReservedForFutureIssuance" name="CommonStockCapitalSharesInitiallyReservedForFutureIssuance" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="rptx_ExercisePricePerShareAsMinimumPercentageOfFairValueOfCommonShare" name="ExercisePricePerShareAsMinimumPercentageOfFairValueOfCommonShare" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_ShareBasedCompensationArrangementByShareBasedPaymentMonthlyVestingRate" name="ShareBasedCompensationArrangementByShareBasedPaymentMonthlyVestingRate" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_AdditionalPaidInCapitalShareBasedPaymentArrangementExercisedOptionsCreditedToCommonShares" name="AdditionalPaidInCapitalShareBasedPaymentArrangementExercisedOptionsCreditedToCommonShares" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueOfStockOptions" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueOfStockOptions" type="num:perShareItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="rptx_NetIncomeLossAttributableToCommonStockholdersBasicAndDiluted" name="NetIncomeLossAttributableToCommonStockholdersBasicAndDiluted" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="rptx_OptionsToPurchaseCommonSharesMember" name="OptionsToPurchaseCommonSharesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_ContractualObligationPeriod" name="ContractualObligationPeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="rptx_ContractualObligationPaid" name="ContractualObligationPaid" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="rptx_SignificantAgreementsAndCommitmentsLineItems" name="SignificantAgreementsAndCommitmentsLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_SignificantAgreementsAndCommitmentsTable" name="SignificantAgreementsAndCommitmentsTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_TheUniversityOfTexasMDAndersonCancerCenterMember" name="TheUniversityOfTexasMDAndersonCancerCenterMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_PreclinicalStudiesAndClinicalTrialsMember" name="PreclinicalStudiesAndClinicalTrialsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="rptx_AccruedExpensesAndOtherCurrentLiabilitiesMember" name="AccruedExpensesAndOtherCurrentLiabilitiesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
</xsd:schema>
