BACKGROUND: In sub-Saharan Africa, adolescent girls and young women are twice as likely to be living with HIV as their male counterparts. This systematic review assesses the impact of the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) program on health-related outcomes, access to services, sexual risk behaviors, and HIV knowledge. METHODS: We searched different databases and conference abstracts from January 2014 to April 2024. We included studies where DREAMS was the primary intervention. We completed meta-analyses using random effects models. Risk of bias and certainty of evidence were assessed. PROSPERO: CRD42022340294. FINDINGS: Seven unique studies were included. The incidence rate ratio (IRR) of HIV incidence was 0.74 (95% CI: 0.63-0.87, 1 study) in DREAMS compared to the comparison group. For self-report of sexually transmitted infections (STI) symptoms, the IRR was 0.84 (95% CI: 0.71-0.98, 1 study). The odds ratio (OR) for awareness of HIV status was 2.34 (95% CI: 1.23-4.44, 1 study). The risk ratio for HIV testing was 1.17 (95% CI: 1.05-1.30, 1 study). For condom use, the OR was 1.22 (95% CI: 0.86-1.72, 1 study). For transactional sex, the OR was 0.99 (95% CI: 0.69-1.41). The OR for the number of sexual partners was 0.74 (95% CI: 0.60-0.91, 1 study). INTERPRETATION: The evidence suggests that DREAMS results in a reduction in HIV incidence and STI symptoms. DREAMS may result in a slight increase in the uptake of HIV testing and a large increase in awareness of HIV status. DREAMS may also reduce the number of sexual partners. Developing a unified and granular evaluation framework would be beneficial in advancing research and generating evidence on DREAMS. FUNDING: No funding source.