Background The strength of a health system—and ultimately the health of a population—depends to a large degree on health worker performance. However, insufficient support to build, manage and optimize human resources for health (HRH) in low- and middle-income countries (LMICs) results in inadequate health workforce performance, perpetuating health inequities and low-quality health services. Methods The USAID-funded Human Resources for Health in 2030 Program (HRH2030) conducted a systematic review of studies documenting supervision enhancements and approaches that improved health worker performance to highlight components associated with these interventions’ effectiveness. Structured by a conceptual framework to classify the inputs, processes, and results, the review assessed 57 supervision studies since 2010 in approximately 29 LMICs. Results Of the successful supervision approaches described in the 57 studies reviewed, 44 were externally funded pilots, which is a limitation. Thirty focused on community health worker (CHW) programs. Health worker supervision was informed by health system data for 38 approaches (67%) and 22 approaches used continuous quality improvement (QI) (39%). Many successful approaches integrated digital supervision technologies (e.g., SmartPhones, mHealth applications) to support existing data systems and complement other health system activities. Few studies were adapted, scaled, or sustained, limiting reports of cost-effectiveness or impact. Conclusion Building on results from the review, to increase health worker supervision effectiveness we recommend to: integrate evidence-based, QI tools and processes; integrate digital supervision data into supervision processes; increase use of health system information and performance data when planning supervision visits to prioritize lowest-performing areas; scale and replicate successful models across service delivery areas and geographies; expand and institutionalize supervision to reach, prepare, protect, and support frontline health workers, especially during health emergencies; transition and sustain supervision efforts with domestic human and financial resources, including communities, for holistic workforce support. In conclusion, effective health worker supervision is informed by health system data, uses continuous quality improvement (QI), and employs digital technologies integrated into other health system activities and existing data systems to enable a whole system approach. Effective supervision enhancements and innovations should be better integrated, scaled, and sustained within existing systems to improve access to quality health care.