Project Summary American Indian communities have been greatly affected by the opioid epidemic with many communities being overwhelmed by opioid use and opioid overdose. Among all racial/ethnic groups in the U.S, American Indians and Alaska Natives have the second highest rate of overdose fatalities from all opioids and second and third highest overdose fatality rates from heroin and synthetic opioids. As with other parts of the country, opioids are the main driver of drug overdose deaths in California. Within Southern California, surveillance data indicates that areas encompassing American Indian reservations have experienced some of the highest age- adjusted rates of opioid-related overdose deaths, hospitalization, and emergency department visits. While there have been efforts to curtail the opioid crisis, much of this work has focused on population-level strategies without enough focus on the community dynamics and local-level context of opioid use. The overarching goal of this study is to characterize the changing etiology of opioid misuse and overdose risk among Southern California American Indian (AI) adults by implementing research methods to promote community engagement and inform a timely public health response to the opioid epidemic. Over a 4-year period, we will collect locally relevant data from diverse sources (80 interviews, 200 surveys, and population-level data on opioid overdose fatalities) to capture emerging patterns of risks and triangulate that information to inform the planning and allocation of prevention and treatment services for AI adults. Our study will be guided by the following Specific Aims: 1. Identify the epidemic profile of individuals at risk for opioid misuse and opioid overdose; 2. Examine community assets and capacity to address prevention and treatment of opioid use/misuse and resulting overdose; and 3. Develop community-based surveillance tool to inform community action towards reducing opioid overdose fatalities. By combining multiple information sources, a more comprehensive analysis and accurate picture of the opioid crisis can be generated. The public health significance of this study will be to continuously assess the environment contributing to opioid misuse and overdose risk across different social and geographical settings among AI Tribes. We anticipate that our findings will inform the short-term and long-term planning of prevention and treatment services that are responsive to the needs of California Tribes.