Urbanization and climate change are the two major environmental challenges of the 21st century. The dramatic expansion of cities around the world creates new conditions for the spread, surveillance, and control of infectious diseases. In particular, urban growth generates pronounced spatial heterogeneity within cities, which can modulate the effect of climate factors at local spatial scales in large urban environments. Importantly, the interaction between environmental forcing and socioeconomic heterogeneity at local scales remains an open area in infectious disease dynamics, especially for urban landscapes of the developing world. A quantitative and conceptual framework on urban health with a focus on infectious diseases would benefit from integrating aspects of climate forcing, population density, and level of wealth. In this paper, we review what is known about these drivers acting independently and jointly on urban infectious diseases; we then outline elements that are missing and would contribute to building such a framework.