Urban agriculture (UA) can be used as an action to promote sustainability in cities and inform public health policies for urban populations. Despite this growing recognition, its implementation still presents challenges in countries in the Global North and Global South. Background: In this context, this systematic review aims to identify the development of frameworks for the implementation of UA as a sustainable action and its main opportunities and shortcomings in meeting urban socio-environmental demands. Methods: In this review, using the PRISMA protocol, we evaluated 26 studies on the interplay between UA and sustainability surveyed on the Web of Science to provide an overview of the state of the art. Conclusions: In summary, it was possible to identify many key challenges in UA adoption, which regard air and soil contamination, availability of green areas, layout of urban infrastructure, food distribution, among others. Due to numerous socio-economic and environmental contextual factors in cities, especially when comparing realities of the Global North and Global South, there is a need to develop a model that can be adaptable to these different contexts. Thus, it is recognized that the concept of sustainability does not present a universal understanding and that in its search it could be argued that one of the most important gaps is still to address social issues in relation to environmental ones.