Objective: American Indian and Alaska Native (AIAN) youth demonstrate significant substance use and mental health disparities and represent a highly underserved population with regard to effective services. A community-based needs assessment study of urban and rural AIAN youth throughout California was conducted to inform the development of community-based, culturally relevant opioid and substance use services. This study examined AIAN youth experiences with opioid and other substance use disorders (OUD/SUD) in their communities, utilization of existing programs, and service system recommendations. Method: Fifteen focus groups were conducted in partnership with urban and rural/reservation health programs, and AIAN serving community-based organizations throughout California with youth ranging from 13 to 18 years of age. Focus groups were recorded and professionally transcribed, then coded using NVivo qualitative data analysis software. An a priori coding structure was refined through a data-informed, iterative process until a final coding structure was agreed upon to characterize data. Results: Findings demonstrate the need for OUD/SUD services that integrate cultural beliefs and practices, incorporate attention to family and community risk and resiliency factors, provide effective outreach and education, and focus on the development of holistic wellness and positive development for AIAN youth. This study also provides a model for conducting a needs assessment using community-based participatory methods to inform effective service development that more directly responds to community-identified needs. Conclusion: Findings indicate that future services and interventions should incorporate a focus on promoting overall wellness and positive youth development in order to prevent or promote recovery from opioid or other substance abuse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).