Mental health challenges among adolescent students are a growing concern worldwide, influenced by various demographic and environmental factors. This study explores the impact of gender and locale differences on the mental health status of adolescent students, aiming to identify patterns and disparities that can inform targeted interventions. Using a cross-sectional survey design, data were collected from 1,200 students aged 13 to 18 across urban and rural schools. Standardized mental health assessment tools were employed to evaluate levels of anxiety, depression, and stress. Statistical analyses, including multivariate regression and interaction effects, were used to examine the influence of gender and locale on mental health outcomes. Results indicate significant differences, with female students reporting higher rates of anxiety and depression, especially in urban settings, while rural students exhibited increased stress related to socioeconomic and educational challenges regardless of gender. These findings highlight the complex interplay between gender and environmental factors in adolescent mental health and underscore the need for tailored mental health programs that consider these variables. The study concludes that policymakers and educators should prioritize gender-sensitive and locale-specific mental health strategies to effectively support adolescent well-being.