Abstract Background: Simulation-based training (SBT) is widely adopted in health professions education to improve skill acquisition, clinical reasoning, and readiness for practice. Evidence, however, remains dispersed across professions and simulation modalities. Objective: To synthesize evidence from PubMed Central original studies on the effectiveness of SBT across dental assisting, medical laboratory education, pharmacy, nursing, obstetrics & gynecology (OB/GYN), and radiology. Methods: A PRISMA-aligned systematic review was conducted using PMC (searched February 2, 2025). Eligible studies were original quantitative evaluations of SBT (including standardized patient simulation, mannequin-based simulation, virtual simulation, AR/VR, and computer-based simulation) involving learners in the target professions. Outcomes included knowledge, skill performance, competency assessments, pass rates, time metrics, and learner perceptions. Data were extracted into standardized tables and synthesized narratively due to heterogeneity. Results: Ten original studies met eligibility criteria: dental assisting (n=1), medical laboratory (n=1), pharmacy (n=2), nursing (n=2), OB/GYN (n=1), radiology (n=2), plus one multi-professional computer-simulation evaluation (n=1). Across professions, SBT consistently improved procedural/communication performance and competency-based outcomes compared with baseline or traditional instruction. Stronger gains were observed when SBT included structured supervision, deliberate practice, and performance assessment. Conclusion: Within PMC-indexed original studies, SBT demonstrates effectiveness in improving skill-based outcomes across multiple health professions. Future research should prioritize standardized outcome measures, longer follow-up, cost-effectiveness, and evidence of transfer to workplace performance.