In Tanzania, HPV vaccination coverage among out-of-school (OOS) adolescent girls aged 9–14 remains low despite national programme progress. As part of the SHARP mixed-methods implementation research study, 69 key informant interviews with health workers and managers in Mbeya and Arusha identified layered barriers to reaching OOS girls, including complex recruitment procedures, transport and distance constraints, high community mobility, seasonal inaccessibility, cultural norms, and peer-driven vaccine hesitancy. Proposed mitigation strategies include deploying community health workers to trace nomadic families, designing youth-friendly facility spaces, integrating HPV vaccination with sexual and reproductive health, nutrition, and other adolescent services at community bonanzas and outreach events, and leveraging local government and private sector partnerships. The findings underscore that reaching OOS adolescents requires integrated, context-adapted approaches that maximize every health contact opportunity.