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Background: Depression is a prevalent and debilitating mental health issue among adolescents. This study aims to investigate the various factors associated with depression among adolescents, enrolled in educational settings aged 15 to 19 in Karachi, Pakistan. Methods: A total of 250 participants were included in the study. Depression levels were assessed using the Hamilton Depression Rating Scale, and participants were categorized by age, gender, educational level, family background, and various psychosocial variables. Data were analyzed using statistical tests to identify significant associations. Results: The study found that 52.8% of participants experienced depressive symptoms. Females exhibited a higher prevalence of depression, 32.4% with a significant increase in symptoms among those above 18 years of age, 26.4%. Additionally, social media usage showed a complex relationship with depression, 4 hours of use with 60.6% and up to 6 or more hours of use with 60.4% prevalence; and the excessive comparisons with online influencers correlating with higher depression risk, 68.4%. 65% (26 out of 40) of those students who found their parents to be Authoritarian; and those perceiving presence of gender differences applied within their household, 12.0% (81.1% within the variable) (p=0.000), were also associated with depression. Other contributing factors included a family history of depression, 20% with a p-value of 0.016; the perception of mental health as a taboo subject, 23.2% with p=0.000; body image dissatisfaction, 24% with p=0.001; and poor appetite, 10.8% with p=0.004. Conclusion: The findings of this study highlight the multifaceted nature of depression among adolescents in Karachi addressing this issue requires a comprehensive approach involving parents, schools, and healthcare providers. Strategies should encompass emotional support, mental health programs, and tailored interventions targeting individual needs. Initiatives involving parents, schools, and healthcare providers are essential to improving the well-being of school-going adolescents in Karachi. [ABSTRACT FROM AUTHOR]