Objective To systematically review the application of escape room game (ERG) in interprofessional medical education, so as to provide references for optimizing interprofessional education and enhancing team collaboration and interprofessional core competency. Methods Relevant literature published from January 2007 to September 2025, was retrieved from PubMed, Embase, Web of Science, EBSCO, Cochrane Library, SinMed, CNKI, Wanfang Data Knowledge Service Platform, and VIP databases for analysis, then included literature was analyzed and summarized. Results Fourteen studies were included. ERG was conducted online or offline with diverse themes to improve interprofessional collaboration and communication skills, strengthen interprofessional awareness, and achieve a comprehensive improvement in team quality. Outcomes indicators included subjective feedback of the participants, the scores of objective knowledge tests, the assessment of team function, escape rooms and simulated interprofessional collaboration performance. Conclusion The simulation-based model of ERG can make up for the deficiencies in teamwork and situational engagement inherent in traditional interprofessional medical education. By providing an immersive experience, it enhances participants′ communication, decision-making, and collaboration skills. When combined with structured debriefing, it strengthens professional role awareness, thereby offering an innovative pathway for cultivating compound nursing talents.