Background: Elements of the physical environment have been shown to influence health behaviors including drug use and overdose mortality. Throughout the opioid epidemic in the United States, rural regions have been disproportionately affected by opioid overdose. Although the relationship between the urban built environment and opioid overdose has been established, little is known as to how trends may differ in rural areas. Methods: Risk terrain modeling was used as a spatial analytical approach to assess environmental features that significantly increase the risk of opioid overdose in Jefferson County, Alabama. Spatial risk assessments were conducted for urban and rural regions as well as for the county as a whole. Criminogenic, opioid-related, and community variables were included and compared across spatial risk models. Results: The geographic context, rural or urban, influenced the relationship between environmental features and opioid overdose. In rural areas, community features such as bus stops and public schools were related to the occurrence of opioid overdose. In urban areas, inpatient treatment centers, transitional living facilities, express loan establishments, and liquor vendors were significantly related to the locations of opioid overdose. Conclusion: Risk terrain modeling can be used to locate high-risk areas for opioid overdose while identifying factors that are contributing to the risk of events occurring in communities. The patterns of overdose risk differ in rural and urban contexts and may be used to inform the placement of treatment and prevention resources.