BACKGROUND: Recent research has demonstrated that domains of social determinants of health (SDOH) (e.g. air pollution and social context) are associated with psychosis. However, SDOHs have often been studied in isolation. This study investigated distinct exposure profiles, estimated their associations with persistent distressing psychotic-like experiences (PLE), and evaluated whether involvement in physical activity partially explains this association. METHODS: Analyses included 8,145 young adolescents from the Adolescent Brain and Cognitive Development Study. Data from the baseline and three follow-ups were included. Area-level geocoded variables spanning various domains of SDOH, including socioeconomic status, education, crime, built environment, social context, and crime, were clustered using a self-organizing map method to identify exposure profiles. Generalized linear mixed modeling tested the association between exposure profiles and persistent distressing PLE and physical activities (i.e. team and individual sports), adjusting for individual-level covariates including age, sex, race/ethnicity, highest level of parent education, family-relatedness, and study sites. RESULTS: Five exposure profiles were identified. Compared to the reference Profile 1 (suburban affluent areas), Profile 3 (rural areas with low walkability and high ozone), and Profile 4 (urban areas with high SES deprivation, high crime, and high pollution) were associated with greater persistent distressing PLE. Team sports mediated 6.14% of the association for Profile 3. CONCLUSIONS: This study found that neighborhoods characterized by rural areas with low walkability and urban areas with high socioeconomic deprivation, pollution concentrations, and crime were associated with persistent distressing PLE. Findings suggest that various social-environmental factors may differentially impact the development of psychosis.