Despite awareness of the role of drug use in shaping sex worker/client interactions, these dynamics remain poorly understood in the context of illicit fentanyl-driven overdose epidemics. This study examined sex workers’ experiences negotiating client interactions amidst a toxic drug supply in Vancouver, Canada. Findings draw from two ethnographic studies. The first, conducted between December 2016 and May 2017, examined the rapid implementation of several low-threshold supervised consumption sites. The second investigated experiences of women accessing a women-only site from May 2017 to June 2018. Data included 200 hours of fieldwork and in-depth semi-structured interviews with 34 street-based sex workers who use illicit drugs. Data were analysed thematically with attention to the risk environment. Participants described providing harm reduction services to clients as a means to reduce overdose-related risks, thus increasing sex workers’ hidden labour. Participants, comments regarding criminalisation and stigma surrounding drug use and sex work indicated a reticence to report overdoses, thereby potentially increasing the risks of overdose-related harms, including death. There is an urgent need for sex worker-led overdose prevention strategies that prioritise health and safety of sex workers and their clients with specific attention to how the criminalisation of particular drugs, practices and people contributes to overdose-related risks.