Health determinants might play an important role in shaping the impacts related to long-term disasters such as droughts. Understanding their distribution in populated dry regions may help to map vulnerabilities and set coping strategies for current and future threats to human health. The aim of the study was to identify the most vulnerable municipalities of the Brazilian semiarid region when it comes to the relationship between drought, health, and their determinants using a multidimensional index. From a place-based framework, epidemiological, socio-economic, rural, and health infrastructure data were obtained for 1135 municipalities in the Brazilian semiarid region. An exploratory factor analysis was used to reduce 32 variables to four independent factors and compute a Health Vulnerability Index. The health vulnerability was modulated by social determinants, rural characteristics, and access to water in this semiarid region. There was a clear distinction between municipalities with the highest human welfare and economic development and those municipalities with the worst living conditions and health status. Spatial patterns showed a cluster of the most vulnerable municipalities in the western, eastern, and northeastern portions of the semiarid region. The spatial visualization of the associated vulnerabilities supports decision making on health promotion policies that should focus on reducing social inequality. In addition, policymakers are presented with a simple tool to identify populations or areas with the worst socioeconomic and health conditions, which can facilitate the targeting of actions and resources on a more equitable basis. Further, the results contribute to the understanding of social determinants that may be related to medium- and long-term health outcomes in the region.