OBJECTIVES: Increasing obesity rates and accelerating climate change represent two global health challenges shaped by lifestyle change and human environmental modifications. Yet, few studies have considered how these issues may interact to exacerbate disease risk. METHODS: In this theory article, we explore evidence that obesity-related disease and climatic changes share socio-ecological drivers and may interact to increase human morbidity and mortality risks. Additionally, we consider how obesity-climate change interactions may disproportionately affect vulnerable populations and how anthropological research can be applied to address this concern. RESULTS: Interactions between heat stress and cardiometabolic disease represent an important pathway through which climate change and obesity-related morbidities may jointly impair health. For example, individuals with higher body fatness and obesity-related metabolic conditions (eg, type 2 diabetes) exhibit a reduced ability to dissipate heat. The risk of poor health resulting from these interactions is expected to be heterogeneous, with low- and middle-income countries, individuals of lower socioeconomic status, and minority populations facing a greater disease burden due to relative lack of resource access (eg, air conditioning). Moreover, older adults are at higher risk due to aging-associated changes in body composition and loss of thermoregulation capabilities. CONCLUSIONS: Few policy makers appear to be considering how interventions can be designed to simultaneously address the medical burden posed by increasing obesity rates and climate change. Anthropological research is well situated to address this need in a nuanced and culturally-sensitive way; producing research that can be used to support community resilience, promote holistic well-being, and improve health outcomes.