Globally, agri-food systems face rising pressure from climate change, population growth, and economic structural shifts, raising worries about the capacity of food systems. Africa holds a crucial role in this worldwide issue due to its swiftly increasing population, significant reliance on agriculture for survival, and ongoing susceptibility to food insecurity and malnutrition. This systematic review explores the impact of economic, cultural, and institutional factors on the shift of Africa’s agri-food systems toward sustainable regional food security. A comprehensive analysis was conducted on 106 peer-reviewed articles published from 2010 to 2024, adhering to PRISMA guidelines. The approach utilized thematic synthesis and descriptive statistical analysis to derive insights on indicators of food security, efficiency in agriculture, and the prevalence of malnutrition. The analysis shows significant regional disparities: Northern and Southern Africa demonstrate comparatively better system efficiency and food security, due to enhanced infrastructure, institutional backing, and economic stability. The results also indicate that economic elements, especially agricultural value chain development, productivity, and access to finance, are significantly linked to enhanced food security, whereas the quality of institutions and governance effectiveness serve a crucial enabling function. Cultural dynamics, such as dietary habits and gender roles, greatly impact food usage and nutrition, particularly in East and West Africa. Significant regional disparities continue, with North and Southern Africa showing comparatively better institutional and economic performance, while Central Africa is dealing with increased vulnerabilities. The assessment emphasizes the significant connections with the Sustainable Development Goals (SDGs), especially SDG 2 (Zero Hunger), SDG 12 (Responsible Consumption and Production), and SDG 13 (Climate Action), highlighting the importance of Agri-food transformation in Africa’s development agenda. Additionally, the examination highlights the increasing significance of climate-smart farming, circular economy approaches, and inclusive policy structures in influencing food system durability and rural economies. The research concludes that Africa’s Agri-food transition necessitates diverse, region-tailored strategies based on economic feasibility, cultural relevance, and institutional changes. It emphasizes the need for improved policy alignment, inter-regional knowledge sharing, and data-driven innovation to secure a fair and sustainable Agri-food future for the continent. This review adds to the body of knowledge by presenting a systems-oriented, region-specific perspective on Africa’s Agri-food transition, supplying data to guide cohesive policy formulation, focused investment, and subsequent research directed at ensuring sustainable food and nutrition security in Africa.