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Adolescence is a critical period for the onset of mental health problems and risky behaviors such as substance use. Although culturally adapted evidence-based programs (EBPs) are promising for prevention, the barriers and facilitators shaping adaptation remain underexplored, particularly from a multisectoral perspective.

This study examines the barriers and facilitators involved in the cultural adaptation of prevention programs targeting adolescent substance use and common mental health problems.

A qualitative secondary analysis was conducted using inductive qualitative content analysis of 22 semi-structured interviews with actors from three quadruple helix sectors: 6 Academia, 6 Nongovernmental organizations, and 10 Public administration, across multiple countries. Participants were recruited through stakeholder mapping, purposive-convenience sampling, and snowball recruitment based on their roles in adapting, implementing, evaluating, or funding prevention programs. Limited recruitment in the business sector led to its exclusion from the analytic sample.

Cultural adaptation was hindered by a weak prevention culture, limited and contextually mismatched EBP uptake, conceptual and methodological ambiguity, weak evaluation, limited or unstable resources, political and institutional instability and burden, and difficulties with collaboration, knowledge transfer, and initial engagement with the target population. It was facilitated by recognition of the culture's importance, institutional and policy alignment, evidence-based and collaborative funding criteria, intersectoral synergy and collaboration with target populations, and practical supports for engagement.

Cultural adaptation is a systemic and relational process shaped by methodological, organizational, institutional, and intersectoral conditions. Strengthening it requires practical methodological support, institutional and policy commitment, and sustained participatory and cross-sector approaches.