Climate and society are co-evolving in a manner that could place more vulnerable populations at risk from weather-related stressors. Despite hazard mitigation efforts and scientific and technological advances, extreme weather events continue to cause substantial losses throughout the world. Studies show that weather extremes often have differential consequences among geographic locations and population groups, because the impacts of extreme weather result from complex interactions among physical and human systems across spatial and temporal scales. As global warming patterns continue, researchers anticipate increases in the severity, frequency and duration of some types of extreme weather events. This presentation will synthesize current interdisciplinary knowledge about extreme weather, discuss projections of changes in weather extremes with anthropogenic climate change, and demonstrate how social vulnerability, coping, and adaptation shape the societal impacts of extreme weather. We will highlight critical gaps where work is needed in order to improve outcomes of extreme weather. We present a research framework that aims to fill these gaps and integrates physical and social science perspectives on climate change, extreme weather, and its impacts to examine how macro-scale drivers, extreme weather conditions, local-level social vulnerability, and coping and adaptation decisions interact to influence societal outcomes. Drawing on examples from recent and ongoing research on extreme heat and urban health in several North American cities, we will demonstrate that local-level assessments are necessary to understand the complex interplay between the social and physical dimensions of extreme heat and to improve heat-health outcomes.