Over the years, drug overdose deaths have steadily increased in the Appalachian region, which is known for having a high blue-collar job composition. This study examines drug overdose related deaths and their relationship with blue-collar jobs. Annual county level data which describes 13 U.S. states in the Appalachian region was collected to investigate the relationship between the drug overdose mortality rate and blue-collar jobs. In-order to measure blue-collar job composition, the total employment percentage of mining, quarrying, oil and gas extraction, construction, and manufacturing were used. Ultimately, the results show that counties with a higher employment percentage in mining, quarrying, oil and gas extraction have a higher drug overdose mortality rate. Conversely, counties with a higher employment percentage in construction or manufacturing have a lower drug overdose mortality rate.