Background: Adolescent mental health and substance misuse is a growing issue, disproportionately affecting diverse youth and those in low-resourced, high-stress environments. Yet, despite recent advances in evidence-based practices for adolescent substance use, perpetuating factors remain under-explored and marginalized, and underserved groups continue to be underrepresented. The current study aimed to investigate sociocultural factors impacting substance misuse and treatment outcomes. Methods: Data from adolescents receiving combined mental health and substance misuse treatment at a regional safety-net hospital were analyzed. Using Latent Class Analysis (LCA), demographic variables including insurance coverage, area deprivation, race, ethnicity, age, gender, court involvement, and primary mental health diagnoses were used to identify unique adolescent subgroups based on these different sociocultural risk factors. Identified classes were tested as predictors of treatment engagement, length of treatment, future service utilization, substance misuse, and urine drug screen results. Results: Five unique subgroups were identified, differentially impacting substance misuse, future service utilization, and treatment outcomes. Conclusions: These results highlight the need for improved access to resources for adolescents who have been marginalized and traditionally underserved. Furthermore, the identified subgroups can inform future research and practice.