Background: Substance use, particularly injection drug use, continues to fuel the HIV/HCV (hepatitis C virus) epidemics in San Juan, Puerto Rico (PR). Aim: This article examines individual and sociostructural factors that affect HIV/HCV risk among people who use drugs (PWUD) living with or at risk for HIV/HCV in San Juan, PR. Findings were used to inform a community-level intervention to enhance HIV care access and retention for this population. Method: A rapid ethnographic assessment in collaboration with a community-based organization was conducted. Data collection took place between June and December 2013 and included field observations, 49 unstructured interviews with PWUD, and 19 key informant interviews with community stakeholders. Fieldnotes, photographs, and interview transcripts were analyzed for recurrent themes and to address the intervention-planning needs. Study results are presented as fieldnote excerpts, direct quotes from interviews, and photographs. Results: Findings suggest that PWUD in PR face myriad challenges that affect HIV/HCV risk and hinder linkage to and retention in care. Results describe a layered risk environment where PWUD encounter many barriers to prevention, care, and treatment such as transience, social isolation, stigma, limited housing options, and inadequate medical and substance use disorder treatment services. Discussion: These observed circumstances provide an empirical basis for the development and evaluation of comprehensive interventions that may serve to reduce barriers to care and link individuals to other supportive services. Conclusion: New approaches and comprehensive interventions are needed to break the structures that perpetuate risk and lack of engagement and retention in HIV care and substance use disorder treatment in San Juan.