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Background: HIV remains a leading cause of death for adolescents and young people aged 10-24 years. HIV prevention requires multisectoral approaches that target adolescents and young people, addressing HIV risk pathways (e.g., transactional sex, gender-based violence, and school attendance) through bundled interventions that combine economic strengthening, health capabilities, and gender equality education. However, best practices are unknown because evidence on multisectoral programming targeted to adolescents and combining these components has not been systematically reviewed., Methods: We conducted a systematic review to summarize the evidence on bundled interventions combining health and economic strengthening components for adolescents and young people and their effects on HIV/STI incidence and risk factors. We included studies from Africa published between 2005 and 2023, combining at least one economic strengthening and one health component, directed toward adolescents and young people aged 10-24 years. Included studies measured programmatic impacts on primary outcomes: HIV and STI incidence/prevalence; and mediators as secondary outcomes: sexual behaviours, sexual and reproductive health, school attendance, health-seeking behaviours, and violence. We conducted key word searches in PubMed, EMBASE, and Web of Science, imported titles/abstracts from the initial search, and reviewed them using the inclusion criteria. Full texts of selected articles were reviewed and information was extracted for analysis. Findings from the full texts identified were summarized., Results: We reviewed 58 studies, including 43 quantitative studies and 15 qualitative studies, evaluating 26 unique interventions. A majority of studies reviewed were conducted in Eastern and Southern Africa. Interventions reviewed showed a greater number of significant results in improving economic outcomes; mental health and psychosocial outcomes; sexual and reproductive health knowledge and services utilization; and HIV prevention knowledge and testing. They showed fewer significant results in improving outcomes related to HIV incidence/prevalence; sexual risk behaviours; gender-based violence; gender attitudes; education; STI incidence, prevalence and testing; and sexual debut., Conclusions: Our review demonstrated the potential for bundled, multisectoral interventions for preventing HIV and facilitating safe transitions to adulthood. Findings have implications for designing HIV sensitive programmes on a larger scale, including how interventions may need to address multiple strata of the social ecological model to achieve success in the prevention of HIV and related pathways., (© 2024. The Author(s).)