Research in this domain uses a variety of methods, which include nationally and internationally representative longitudinal datasets with multi-modal measures such as surveys, electronic health records, neuroimaging, biosamples, and mobile assessment to examine genetic, individual, social, and neighborhood/community factors that influence the etiology and course of substance use. Our prevention research has increasingly focused on the social and structural determinants of health as a pathway toward advancing health equity among underserved and minoritized populations. On-going research on early intervention for substance use includes evaluating behavioral treatments in diverse populations, testing novel cognitive neuroscience techniques, and developing innovative mobile health interventions, such as personalized “just-in-time” interventions. Our goal for prevention and early intervention is to provide personalized care “when” and “where” it may be most effective.