The SANTINELLES project offers a comparative analysis of urban health in two mid-sized West African cities, Saint-Louis (Senegal) and Bobo-Dioulasso (Burkina Faso). This paper highlights our findings about how the socio-spatial organization in the eight sampled neighborhoods shapes vulnerability to disease. First, we highlight how historical legacies, migration, and social and economic processes have shaped neighborhoods and urban landscapes in these two former colonial cities. Second, we examine how the social networks of local actors are spatially rooted in both cities, contributing to different forms of governance and unequal development dynamics. These findings are triangulated with the clinical and qualitative data of the larger study to analyze how socio-territorial processes materialize in disease morbidity, lack of access to medical care, and illness experience. The data for this paper reflects our grounding in health geography; we used direct observation, sketch maps, and semi-structured interviews with stakeholders, care givers, community organizations and inhabitants.