ABSTRACT HIV incidence is high and persistent among cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men, particularly among those who sell or trade sex. In preparation for an open-label combination HIV pre-exposure prophylaxis (PrEP) program for these groups, we conducted formative research to explore the context of sex work/trade and factors that affect implementation of PrEP interventions. This study analyzed interviews with 20 young (aged 18–26 years) MSM and TGW who sell/trade sex and three sex work venue managers in Bangkok and Pattaya, Thailand. Participants described diverse contexts of sex work/trade, including in multiple informal and formal sex venues. Several participants reported mobility across provinces and out of the country, which led to intermittent sex work/trade. TGW sex workers reported challenges with access and cost of femininizing hormones and limited employment opportunities. Factors that could facilitate or challenge PrEP program implementation included HIV stigma, the role of venue management in sexual health practice, lack of PrEP knowledge, lower perceived HIV risk, and interest in personal health and wellbeing. Program implementers must consider myriad factors to successfully implement PrEP among young MSM and TGW engaged in sex work or trade in Thailand.