The opioid crisis has impacted many regions of the United States, transcending socioeconomic, demographic, and political divides and leading to urgent calls for public health and law enforcement interventions. It has hit both micropolitan and rural smaller communities especially hard, with severe increases in prescription drug-induced fatalities over time. This paper explores socioeconomic determinants and spatial disparities of fatalities caused by drug and opioid overdose (both intentional and unintentional), focusing specifically on rural-urban differences and understanding the separate role of net farm income in the drug overdose crisis. Our panel data analysis of all US counties spanning the 1970-2016 period indicates that rurality, as measured by lower population density, is associated with higher deaths rates. Importantly, while our research suggests that the opioid crises went hand in hand with declining net farm income, the effect appears to be small. Specifically, we estimate that each $10,000 reduction in net income per farm is associated with a 0.04 increase in overdose age-adjusted deaths per 100,000 people. This effect is more prominent in counties with persistent poverty, which also is predominantly rural. Given the pronounced variability in farm financial indicators over time, the relative health of the farm sector in rural areas may warrant more attention if the pressing health crisis is to be addressed effectively.