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This essay makes the argument that racial disparities in health are rooted in political economic processes undergirding racial residential segregation. Mortgage financing is considered a key institutional tool whereby already marginalized people are isolated into degenerative ecological environments. A multilevel root cause conceptual framework, the racism-race reification process (R-cubed-p), is proposed to delineate how structural factors shape the health of individuals through the reification of race. After situating the conceptual roots of R-cubed-p in postcolonial theory, the key components of the conceptual framework are detailed and applied to clarify extant understandings of the distal factors informing racial inequalities in health. Exploratory analysis is presented that links political economies to ethnoracial residential segregation at the neighborhood-level. The essay concludes by considering how individual outcomes are artifacts of the structural reality of race and racism.