ABSTRACT Interprofessional simulation has been linked to improved self-efficacy, communication, knowledge and teamwork skills in healthcare teams. However, there are few studies that synthesize learners’ perceptions of interprofessional simulation-based approaches and barriers or facilitators they encounter in such learning approaches. The aim of this review was to explore these issues through synthesis of the published literature on healthcare staff engaging in interprofessional simulation to inform enhancement of instructional design processes. Searches of four major databases resulted in the retrieval of 2,727 studies. Following screening and full-text review, a total of 13 studies were included in the final review and deductive content analysis was used to collate the findings, which were then synthesized using a narrative approach. Three categories of barriers and facilitators were identified: characteristics of the simulation learning process, outcomes of interprofessional simulation, and interprofessional dynamics. Related to the latter, the findings indicate the instructional design of interprofessional simulation-based approaches may benefit from a greater focus on the context of healthcare teams that prioritizes teamwork. Furthermore, greater emphasis on designing realistic clinical situations promotes effectiveness of simulation. It is important to recognize the perspectives of healthcare team members engaging in these learning approaches and how they may affect clinical performance and influence patient outcomes.