This cross-sectional, multicountry review examined how structured research mentorship programs can strengthen Human Resources for Health (HRH) systems across Africa by addressing workforce shortages, inequitable distribution of expertise, and limited institutional capacity. Researchers synthesized evidence from existing programs, including the Consortium for Advanced Research Training in Africa (CARTA), African Mental Health Research Initiative (AMARI), Transforming Health Professions Education in Tanzania (THET), and Nigeria Implementation Science Alliance (NISA), to identify scalable mentorship models. Data were drawn from published reports, policy documents, and organizational case studies between 2010 and 2024. The study explored how mentorship fosters research capacity, improves retention, and supports evidence-based clinical practice, with particular attention to the barriers faced by early-career African researchers. The analysis found that structured mentorship improved research productivity, publication quality, and grant acquisition among mentees, while fostering innovation and collaboration within academic and clinical environments. However, challenges such as limited funding, brain drain, weak digital infrastructure, and hierarchical institutional cultures constrained widespread adoption. Most programs lacked formal evaluation frameworks and equitable geographic distribution. Although several regional models demonstrated promise, external validation of long-term outcomes remains limited.