South Africa is one of the few countries with a documented history of research on femicide. Despite previous research efforts, South Africa, facing an extreme rate of violence, has lacked a comprehensive strategy. This article delves into the specific development of a six-month, phased, research-driven, and consultative approach to create a femicide-specific prevention strategy in South Africa. The process included an expert review, multi-sectoral stakeholder consultations, and a literature review to develop an evidence-based socio-ecological model of femicide drivers and a robust theory of change. A country-level specific was produced inclusive of the diverse and individual experiences of women and the distinguishment between intimate partner and non-intimate partner femicide. Key objectives outlined pertained to strengthening legislation, policy, leadership, and accountability to establish evidence and practice-informed prevention methodologies. In turn, successful implementation of prevention measures relies on evidence-based approaches, intergovernmental collaboration, continued research for innovation, and political leadership.