This systematic review aims to evaluate the effectiveness of systems-based practice (SBP) curricula from the perspective of health professions students and workers. A total of 8468 citations were sourced from six electronic databases and manual searches conducted independently by two researchers, of which 44 studies were eventually included. A meta-analysis using a random effects model and a meta-synthesis using the thematic synthesis approach were conducted. Most studies targeted medical students, residents, and resident physicians from various clinical specialties. Almost half of all studies focused on didactic or knowledge-based interventions to teach SBP. About a third of all studies measured non-self-evaluated knowledge change, clinical abilities, and clinical outcomes. Both meta-analysis and meta-synthesis results revealed positive outcomes of increased knowledge of SBP, increased recognition of SBP as a core competency in one’s profession, and increased application of SBP knowledge in one’s profession. Meta-synthesis results also revealed negative outcomes at the institutional and teacher/health professions level. This review highlights the importance of SBP education and supports the effectiveness of SBP curricula. There is a need to address the negative outcomes at the institutional and teacher/health professions level. Moreover, future studies could investigate the integration of self-assessment outcomes with comparison to some external standard.