While alcohol remains the most widely endorsed substance during adolescence, and various psychosocial risk factors have been identified, unknown are the potential origins for how differences in alcohol related problems emerge among young adults. Applying a bio-psycho-social model to youth alcohol use (AU) prevention research is necessary to identify high impact points of intervention during adolescence before AU related problems emerge in adulthood. Given that both alcohol use and mental health distress emerge in adolescence, investigating relationships between bio-psycho-social factors and AU and related problems in adolescence is critical. We will consider both the risk and protective role of multilevel bio-psycho-social risk and protective factors for AU and mental health during adolescence using the ecodevelopmental framework, including Hispanic youth. Further, understanding bio-psycho-social risk and protective factors in association with AU and related problems will guide interventions that can target multiple bio-psycho-social factors for youth. This proposal will leverage the Adolescent Brain Cognitive Development® (ABCD) Study, a large comprehensive dataset, to advance critical areas of research in AU prevention among youth. A quantitative analysis will test (1) bio-psycho-social factors of AU related problems and mental health, and (2) AU influences on mental (anxiety/depression) in association with cognitive and school performance in youth. This proposal will use ABCD study longitudinal data to identify promotive factors that may buffer risk for AU and related problems influenced by both risk from individual and broader contextual factors. Potential co-emerging differences in mental health among youth will be investigated, and whether mental health (i.e., anxiety/depression) outcomes moderate (i.e., exacerbates) the influence of AU on adolescent cognitive functioning. This proposal will then extend the application of the bio-psycho-social model with community-engaged research approach to conduct a qualitative study with focus groups with Hispanic youth and parents to obtain a response to the ABCD study quantitative findings. Findings will inform hypotheses on future AU prevention research using community-engaged approaches with youth in a future R01. In summary, the quantitative and qualitative studies proposed will investigate the bio-psycho-social factors of risk and protective factors for alcohol use and mental health and subsequent impact on cognitive development. Findings will inform future interventions on AU prevention on timing and the interplay of multilevel bio-psycho-social factors.