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Introduction Metabolicsyndrome (MetS)notably influencesbreast cancerpatho genesis, treatment efficacy, andprognosis. This study investigates theassociation betweenMetS and the rate of pathological complete response (pCR) following neoadjuvantchemotherapy (NACT) inpatientswith locallyadvancedbreastcancer (LABC). Objective TostudytheresponseofNACTinpatientswithLABCwithorwithoutMetS. Materials andMethods In this prospective observational study (June 2022 June2024), 188patientswithLABCplanned forNACTwereenrolled. Participants were stratified into twocohorts basedon theNCEPATP III (National Cholesterol EducationProgramAdultTreatmentPanelIII)Criteria:ArmA(MetS,n¼91)andArmB (non-MetS,n¼97).TheprimaryoutcomewastheachievementofpCR.Associations wereanalyzedusingchi-square tests,withunivariateandmultivariateanalyses to identifypredictivefactors. Results TheoverallpCRratewas20.2%(n¼38/188).Alower,thoughnotstatistically significant,pCRratewasobservedintheMetSgroup(15.4%,n¼14/91)comparedwith the non-MetS group (24.7%, n¼24/97) (p¼0.078). Subgroup analyses revealed significant interactions:HER2-negativepatientswithMetShadasignificantly lower pCRratethantheirnon-MetScounterparts(p¼0.049).Furthermore,premenopausal womenwithoutMetSachievedsignificantlyhigherpCRrates thanpremenopausal womenwithMetS(p¼0.008).Onmultivariateanalysisadjustingforageandmeno pausal status,MetSwasnotanindependentpredictorofpCR(oddsratio:0.65,95% confidenceinterval:0.30–1.39,p¼0.27).ERandHER2statusalonedidnot showa significant independentassociationwithpCR