PROJECT SUMMARY Racial, ethnic, and sexual and gender minority populations are disproportionately impacted by HIV and substance use, with Black men who have sex with men (BMSM) and Black transgender women (TW) bearing a disproportionate burden. However, researchers have yet to synthesize a rigorous and holistic view of how individual and complex factors interact to produce health disparities among minority populations. Therefore, understanding the drivers of health disparities requires a novel approach – one which seeks to understand the social and contextual systems around the most marginalized populations – as it is only through an individual's interactions with their social context that any advantage or disadvantage is conferred. In line with RFA-DA-23- 061, this project proposes innovative observational research across five US cities in order to better understand the social contexts of racial, ethnic, and sexual and gender minority populations, as well as how inequities in those social contexts drive HIV and substance use. Specifically, through in-depth remote network surveys of 2700 racially diverse young men who have sex with men and transgender women (YMSM-TW), we will examine how an individual's social position determines the people and the places they have access to, as well as how supportive or risky these social and contextual environments are and how these connections might pool risk and provide fewer resources to those with marginalized and multiple marginalized identities. In this work we are guided by our systems framework which has been integrated with a literature on how stigma maintains dominance by keeping marginalized populations in, out, and away. We also have a robust plan for community engagement – which includes a Community Engagement Core, the building of Community Advisory Boards across each of our five cities, and the utilization of our models to produce tangible targets for public health intervention. Our approach is well-informed by our prior work. In particular, we hold ample expertise in the modeling of the sexual networks of young racially diverse MSM and TW. Furthermore, this study builds off our prior project chiSTIG where our team is using existing empirical data and community input to create Chicago-specific simulations of how racial differences in how YMSM and transgender women co-locate shapes sexual partnership in ways that pool risk for the most marginalized individuals. Furthermore, our approach is enabled by our expertise in network data capture, specifically our leadership of Network Canvas, an NIH- funded free and open-source network data capture tool. These experiences, as well as our skill in building and leading strong transdisciplinary teams, make this work feasible. Taken together, this project is well-suited to transform the scientific understanding of structural drivers of disparities in HIV and substance use.