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Synergistic associations between social inequities and HIV vulnerabilities – known as a syndemic – are understudied with youth in humanitarian settings. We explored refugee youths' HIV prevention needs in Bidi Bidi Refugee Settlement, Uganda. This multi-methods study involved 6 focus groups and 12 in-depth individual interviews (IDI) with refugee youth (n = 60) aged 16–24, and IDI with refugee elders (n = 8) and healthcare providers (n = 8). We then conducted cross-sectional surveys with refugee youth (16–24 years) (n = 115) to assess: poverty, recent sexual and gender-based violence (SGBV), and condom engagement motivation (CEM) (wanting to learn about condoms for HIV prevention). Multivariable logistic regression was used to estimate adjusted odds ratios for associations between poverty and SGBV with CEM. Qualitative narratives revealed poverty and trauma elevated substance use, and these converged to exacerbate SGBV. SGBV and transactional sex increased HIV vulnerabilities. Among survey participants, poverty and recent SGBV were associated with reduced odds of CEM. The interaction between poverty and recent SGBV was significant: the predicted probability of CEM among youth who experienced both poverty and SGBV was almost half than among youth who experienced poverty alone, SGBV alone, or neither. Findings signal the confluence of poverty, violence, and substance use elevate refugee youth HIV vulnerabilities. [ABSTRACT FROM AUTHOR]