Increasing anthropogenic alteration has resulted in increased exposure to both point and nonpoint source pollution. These exposures are increasingly studied for their role in human diseases, including diseases with known genetic or lifestyle risk factors. This study analyzed associations between a variety of human diseases and trace metals, PCBs, and PAHs in soil, groundwater, sediment, and fish. Contaminant spatial data at the county level from Virginia were used in ArcGIS to identify these associations among socially vulnerable populations. The neurologic and psychiatric disorders and cognitive markers were associated with numerous metals in groundwater/soil and/or aquatic system contaminants. Cancer death rates, fetal deaths, and infant deaths were also related to multiple environmental exposures from both categories of exposure. In contrast, many of the chronic diseases which are primarily attributed to lifestyle showed little association with these exposures with the exception of COPD which did appear to be associated with multiple metal exposures. Asthma showed similar associations compared to COPD. Our data suggest that within the context of socially vulnerable populations, where disease burden is often highest, exposures to metals, PAHs, and PCBs may play a role in the development or exacerbation of several highly prevalent categories of disease. These environmental exposures likely act through a variety of pathways all generally leading to increased oxidative stress, inflammation, or interference with biological systems and a subsequent role in disease development.