Work-related stress has been well-examined among physicians, but little is known about how it might affect drug use or healthcare workers in lower-wage occupations characterized by high job demands and low occupational autonomy (e.g., medical assistants, nursing assistants). We collected data from a diverse sample of healthcare workers (N = 200) and separately examined the cross-sectional relationships between several work-related experiences (i.e., compassion satisfaction, burnout, and secondary traumatic stress) and measures of current drug use (i.e., non-medical use of prescription drugs [NMUPD], cannabis use, and illicit drug use). We then examined for differences in these relationships by occupational level (i.e., prescriber/administrator vs. other healthcare worker). In main effects models, greater burnout and secondary traumatic stress were both associated with higher odds of NMUPD, cannabis use, and illicit drug use (ps < 0.01). Greater compassion satisfaction was associated with lower odds of illicit drug use (p < 0.05), but not with NMUPD or cannabis use (ps > 0.05). There was a significant interaction between secondary traumatic stress and occupational level on NMUPD (p < 0.05) such that there was no relationship among prescribers/administrators, but the likelihood of NMUPD increased with greater secondary traumatic stress among other healthcare workers. Similar trend-level interactions were observed between secondary traumatic stress and occupational level on cannabis use (p < 0.10) and between burnout and occupational level on NMUPD. Burnout and secondary traumatic stress may contribute to drug use, and lower-wage healthcare workers may be especially vulnerable.