Gender-based violence and femicide (GBVF) is a multifaceted complex phenomenon that needs urgent comprehensive attention in South Africa and other similarly or worse-off affected countries. Central to combating and eliminating GBVF starts with a systematic understanding of the drivers of GBVF. The research aims to develop a conceptual framework of drivers of gender-based violence and femicide, which can be applied to different GVBF improvement studies. The conceptual framework was developed using ecological system theory having 20 indicators relating to: microsystem – personal history and individual factors; mesosystem – interpersonal relationships; exosystem – community factors; macrosystem – societal factors; and chronosystem – significant changes over time. The framework interlinking these GBVF drivers allows for the diagnosis of the main drivers of GBVF and estimates its impact on the victims and their families. This, in turn, can help to combat and eliminate GBVF through moderation with GBVF policies and strategies. This study contributes to systematically demystifying of drivers of GBVF, especially in South Africa and similar African countries.