<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-02-23</periodOfReport>

    <issuer>
        <issuerCik>0001826457</issuerCik>
        <issuerName>Monte Rosa Therapeutics, Inc.</issuerName>
        <issuerTradingSymbol>GLUE</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001862930</rptOwnerCik>
            <rptOwnerName>Janku Filip</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>MONTE ROSA THERAPEUTICS, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>321 HARRISON AVENUE, SUITE 900</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02118</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>false</isDirector>
            <isOfficer>true</isOfficer>
            <isTenPercentOwner>false</isTenPercentOwner>
            <isOther>false</isOther>
            <officerTitle>Chief Medical Officer</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2026-02-23</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>S</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>9189</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>19.4973</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>65837</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <ownerSignature>
        <signatureName>/s/ Markus Warmuth, Attorney-in-Fact</signatureName>
        <signatureDate>2026-02-24</signatureDate>
    </ownerSignature>
</ownershipDocument>
