Background Social determinants of health (SDOH) significantly impact preteen health. Unlike prior research which often focused on a limited or selected set of SDOH variables, this study aims to explore the effect of a wide array of unbiased computed SDOH patterns on preteen mental, cognitive, and physical health outcomes. Methods This population-based cohort study analyzed preteens aged 9 to 10 years and their caregivers, who were part of the Adolescent Brain Cognitive Development (ABCD) Study from 2016 to 2021 across 21 sites in 17 states. A comprehensive examination of 84 neighborhood-level, geocoded SDOH variables across 7 domains—bias, education, physical and health infrastructure, natural environment, socioeconomic status, social context, and crime and drugs—was conducted. Hierarchical agglomerative clustering identified distinct SDOH patterns. The study estimated the associations between these SDOH patterns and various developmental outcomes of preteens using mixed-effects linear and logistic regression models. Results Out of 10,504 preteens (median age of 9.9 years at baseline; 52.5% boys and 47.5% girls; diverse racial backgrounds), four SDOH patterns were identified: affluence, high-stigma environment, high socioeconomic deprivation, and high crime and drug sales combined with low education and high population density. The analysis revealed that preteens exposed to high socioeconomic deprivation experienced the most significant adverse outcomes, exhibiting increased internalizing and externalizing mental health issues, lower cognitive performance, and negative physical health indicators compared to those exposed to other SDOH patterns. Conclusion/Interpretation The study underscores the importance of an unbiased, multidimensional analysis of SDOH in understanding its impact on preteen developmental outcomes. The findings highlight that preteens facing socioeconomic deprivation are at a considerable disadvantage, suggesting a critical need for interventions aimed at improving socioeconomic conditions to enhance developmental outcomes for this vulnerable population.