Causal inference regarding the impact of place on health is constrained by limited attention to the biological plausibility of associations. The utility of such evidence also requires demonstrating that place-based exposures precede effects on health. We propose a conceptual framework that integrates time and two plausible biosocial pathways by which the geospatial clustering of social disadvantage might be viewed as causally related to the development of cardiovascular and glycemic disease. The framework distinguishes environmental risk conditions that condition the expression of individual behavioural and psychosocial characteristics, and socioeconomic and material conditions that influence regulatory systems through conscious and non-conscious mechanisms.