Background <p>Psychiatric comorbidity among adolescents meeting diagnostic criteria for substance use disorder (SUD) and/or alcohol use disorder (AUD) is poorly characterised in sub-Saharan African settings. Existing approaches typically quantify co-occurring diagnoses individually rather than identifying distinct configurations of psychiatric burden. The present study applied latent class analysis (LCA) to delineate comorbidity profiles within a substance-affected Nigerian adolescent sample and examined associations between class membership, suicidality, cumulative adversity, and functional impairment.</p> Methods <p>Cross-sectional analysis of 614 adolescents meeting DSM-IV criteria for SUD and/or AUD, drawn from the Lagos Schools Emotional and Behavioral Health Survey (LSEBHS), a population-based survey of 9,437 public secondary school students across 47 schools in Lagos State, Nigeria. Latent class analysis was conducted using five binary psychiatric indicators: major depressive disorder (MDD), any anxiety disorder, conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and psychotic-like experiences (PLE; ≥6 items on the Prodromal Questionnaire-16). Multinomial logistic regression (R3STEP) adjusted for classification uncertainty. All analyses incorporated complex survey sampling weights.</p> Results <p>A three-class solution was retained as optimal (BIC = 2,856.8; entropy = 0.87; all classes ≥ 18.0%). The Low Psychiatric Burden class (48.0%, <i>n</i> ≈ 295) showed uniformly low indicator probabilities. The Internalising-PLE class (34.0%, <i>n</i> ≈ 209) was characterised by elevated MDD (0.74), anxiety (0.68), and PLE (0.61) probabilities. The High Multimorbidity class (18.0%, <i>n</i> ≈ 110) showed high probabilities across all five indicators (MDD 0.91; anxiety 0.84; PLE 0.88; conduct disorder 0.74; ADHD 0.67). Overall, 80.1% of the sample met criteria for at least one co-occurring psychiatric disorder. Past-month suicidal ideation increased monotonically across classes (Low Burden: 3.8%; Internalising-PLE: 11.2%; High Multimorbidity: 18.4%). High cumulative adversity (ACE ≥ 3) was the strongest independent predictor of High Multimorbidity class membership (AOR = 2.88; 95% CI 1.82–4.56). A proof-of-concept screening analysis yielded AUC = 0.79 within-model; against an independent functional impairment criterion, AUC was 0.72, with the 0.07 difference quantifying the circularity effect.</p> Conclusions <p>Psychiatric comorbidity among substance-affected Nigerian adolescents is heterogeneously distributed across three statistically distinct profiles. The High Multimorbidity stratum, comprising approximately one in five adolescents, is characterised by near-universal psychiatric burden, elevated suicidality, and strong associations with cumulative adversity. Longitudinal research is required to clarify developmental pathways and validate these profiles in independent samples.</p> Clinical trial number <p>Not applicable.</p>