Globally, 2.2 billion people rely on groundwater for their water supply, and 2.8 billion use onsite sanitation systems for their sanitation needs. Groundwater contamination from septic systems is a critical public health concern, linked with diseases related to water sanitation and hygiene. Despite the severe impacts of septic systems on groundwater quality, comprehensive global studies remain limited. This study conducted a systematic review of articles published between 2012 and 2023 on topics related to septic systems and groundwater contamination, and 82 peer-reviewed articles met the inclusion criteria. The review identified key contaminants, including E.coli, nitrate, Enterococcus spp., total coliform, ammonium, phosphate, chlorides, and pharmaceuticals. Research on microbial indicators is more prevalent in Africa, while research on nutrients is common in North America. Research on organic contaminants including polyfluoroalkyl substances (PFAS), pharmaceuticals, and personal care products (PCPPs) is limited, particularly in low-and middle-income countries. Critical factors contributing to groundwater contamination include soil, hydrogeological conditions, climate, septic system maintenance and functioning, and septic density. The goal of this study was to comprehensively assess the extent of groundwater contamination resulting from septic system effluents by identifying the major contaminants typically found in affected groundwater sources and exploring the factors contributing to contamination. Identifying the major contaminants and factors related to groundwater contamination from septic systems is crucial for developing effective management strategies to protect groundwater sources.