As human development increases across the globe, wildlife are either pushed out of developed areas or adapt to survive in these novel, human-dominated landscapes. Many mammalian mesopredators, such as the Virginia opossum (Didelphis virginiana), have adapted to living alongside human development and take advantage of human-subsidized food, water, and shelter. Understanding how dominant and subordinate mesopredators co-exist across natural and developed areas will provide valuable insight into how urban wildlife communities are structured. Our objective was to evaluate how Virginia opossum occupancy, abundance, and activity was associated with both human development and the relative abundance of their predators. We found that opossum occupancy was positively associated with an index of human activity (anthropogenic sound), but at very high levels of housing density, opossum occurrence decreased. Opossum in heavily forested areas were more likely to be detected in areas with higher predicted anthropogenic sound. In areas with a high density of human housing, opossum relative abundance increased even in situations where predator abundance also increased. However, at low or moderate levels of housing density, opossum abundance did not increase although predator abundance did. Opossum shifted their activity to being active earlier in the evening in the presence of high predator abundance. These results confirm that the Virginia opossum is a successful urban-exploiter. Future research should evaluate if the association of Virginia opossum with urban areas is a direct result of human subsidized resources and/or reduced mortality caused by altered predator-prey dynamics.