Agri-food systems (AFS) have been central in the debate on sustainable development. Despite this growing interest in AFS, comprehensive analyses of the scholarly literature are hard to find. Therefore, the present systematic review delineated the contours of this growing research strand and analyzed how it relates to sustainability. A search performed on the Web of Science in January 2020 yielded 1389 documents, and 1289 were selected and underwent bibliometric and topical analyses. The topical analysis was informed by the SAFA (Sustainability Assessment of Food and Agriculture systems) approach of FAO and structured along four dimensions viz. environment, economy, society and culture, and policy and governance. The review shows an increasing interest in AFS with an exponential increase in publications number. However, the study field is north-biased and dominated by researchers and organizations from developed countries. Moreover, the analysis suggests that while environmental aspects are sufficiently addressed, social, economic, and political ones are generally overlooked. The paper ends by providing directions for future research and listing some topics to be integrated into a comprehensive, multidisciplinary agenda addressing the multifaceted (un)sustainability of AFS. It makes the case for adopting a holistic, 4-P (planet, people, profit, policy) approach in agri-food system studies.