Objective To integrate the best evidence on polypharmacy management in patients with cardiometabolic multimorbidity, so as to provide an evidence-based basis for clinical practice.Methods Evidence on domestic and international polypharmacy management in patients with cardiometabolic multimorbidity in decision support systems, guideline websites, databases, and websites of professional organizations was systematically searched from the establishment of the databases to January 20,2025, and investigators performed quality evaluation, evidence extraction, and summarization of studies that met the criteria.Results A total of 14 publications were included, consisting of 2 guidelines, 7 expert consensus statements, 4 systematic reviews, and 1 evidence summary.Twenty three pieces of best evidence on polypharmacy management in patients with cardiometabolic multimorbidity were summarized and categorized into 7 aspects:team building, medication assessment, prescription streamlining, individualized medication strategies, home management, health education, and monitoring and follow-up.Conclusion The summarized evidence for the management of polypharmacy in patients with cardiometabolic multimorbidity can provide an evidence-based basis for clinical practice.It is suggested to apply and validate the evidence in conjunction with the actual conditions of the patients during evidence translation.