This scoping review aims to explore the interplay between substance use (SU) and HIV in Latin America (LA). Database searches yielded 3481 references; 196 were included. HIV prevalence among people who used substances (PWUS) ranged from 2.8–15.2%. SU definitions were variable throughout studies, and thus data were not easily comparable. In 2019, only 2% of new HIV infections were attributed to injection drug use (IDU) in LA. Factors associated with HIV among PWUS included being female, IDU and homelessness, and PWUS were likely to engage in risky sexual behaviors, start antiretroviral treatment late, have poor adherence, have treatment failure, be lost to follow‐up, have comorbidities, and experience higher mortality rates and lower quality of life, as has been reported in PLWH with SU in other regions. Five intervention studies were identified, and only one was effective at reducing HIV incidence in PWUS. Interventions in other regions have varying success depending on context‐specific characteristics, highlighting the need to conduct more research in the LA region. Though progress has been made in establishing SU as a major concern in people living with HIV (PLWH), much more is yet to be done to reduce the burden of HIV and SU in LA.