HIV remains elevated among female sex workers (FSW) globally, with a number of structural (e.g., poverty, access to care) factors driving these persistently high rates. Pre-exposure prophylaxis (PrEP), a user-controlled prevention method, is a promising means of empowering vulnerable populations to protect themselves and enhance agency. Yet there is a dearth of PrEP research and interventions targeting cisgender women in the United States, and even fewer aimed to reach FSW. We developed and implemented a multifaceted PrEP pilot intervention, the Promoting Empowerment And Risk Reduction (PEARL) study, to meet this gap. This paper describes the development process and nature of a community-informed intervention for tenofovir/emticitrabine (TDF/FTC) pre-exposure prophylaxis engagement among street-based cisgender FSW in Baltimore, Maryland, U.S. In the course of the study's implementation, structural, programmatic, and medical barriers have already posed significant barriers to full engagement. PEARL implemented a number of strategies in an effort to counter barriers and facilitate increased success of PrEP uptake and maintenance. The study will provide critical insights into the nature of intervention components that could help FSW to initiate PrEP and reduce PrEP care cascade gaps.