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The built environment of cities is complex and influences social and environmental determinants of health. In this study we, 1) identified city profiles based on the built landscape and street design characteristics of cities in Latin America and 2) evaluated the associations of city profiles with social determinants of health and air pollution. Landscape and street design profiles of 370 cities were identified using finite mixture modeling. For landscape, we measured fragmentation, isolation, and shape. For street design, we measured street connectivity, street length, and directness. We fitted a two-level linear mixed model to assess the association of social and environmental determinants of health with the profiles. We identified four profiles for landscape and four for the street design domain. The most common landscape profile was the “proximate stones” characterized by moderate fragmentation, isolation and patch size, and irregular shape. The most common street design profile was the “semi-hyperbolic grid” characterized by moderate connectivity, street length, and directness. The “semi-hyperbolic grid”, “spiderweb” and “hyperbolic grid” profiles were positively associated with higher access to piped water and less overcrowding. The “semi-hyperbolic grid” and “spiderweb” profiles were associated with higher air pollution. The “proximate stones” and “proximate inkblots” profiles were associated with higher congestion. In conclusion, there is substantial heterogeneity in the urban landscape and street design profiles of Latin American cities. While we did not find a specific built environment profile that was consistently associated with lower air pollution and better social conditions, the different configurations of the built environments of cities should be considered when planning healthy and sustainable cities in Latin America.