Abstract
<title>Abstract</title> <p> <bold>Background</bold> Adolescence carries a high risk for mental health challenges and substance use. Hospital-based data from Nigeria are scarce. This study determined the prevalence, association, and predictors of mental health challenges and substance use among adolescents in a Family Medicine Clinic, University of Benin Teaching Hospital, Benin City. <bold>Methods</bold> A cross-sectional study was conducted among 385 randomly recruited adolescents aged 10–19 years. Standardized instruments used: Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder-7 for anxiety, and the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) tool for substance use risk. Data were analysed with SPSS version 21. Chi-square/Fisher’s exact test for bivariate associations. Multivariable logistic regression to identify predictors. Significance at p < 0.05. <bold>Results</bold> Overall prevalence was 24.7%. Depression was 22.3% and anxiety 11.8%. At-risk substance use was 3.9%, with female vulnerability, and it was the strongest predictor of mental health challenges, AOR 15.508, 95% CI 4.145–58.014, <italic>p</italic> < 0.001. Living alone, AOR 0.04, 95% CI .005–.334, <italic>p</italic> = 0.003, and earning income, AOR .298, 95% CI .099–.903, <italic>p</italic> = 0.032, were associated with lower odds. Age, sex, and education were not significant. <bold>Conclusions</bold> One in four adolescents in this primary care setting had mental health challenges or substance use risk. The strong association with substance use and the influence of economic factors, and the unexpected associations with patient living arrangement and female vulnerability emphasize the need for context-specific, family-focused, gender-responsive interventions, and routine mental health screening should be integrated in Family Medicine Clinics. </p>