Substance use among secondary school students is a growing concern with significant implications for public health. This study aimed to identify the risk factors associated with substance use in a community of secondary school students in Aden Governorate, Yemen. A cross-sectional study was conducted among secondary school students in Aden governorate, using a structured questionnaire to collect data on potential risk factors for substance use. The questionnaire included measures of Peer Pressure, Academic Performance (GPA), Parental Monitoring, as well as self-esteem towards drug use. The Self-esteem among secondary students was measured using Rosenberg's Self-Esteem Scale. Descriptive and inferential statistical analyses were performed to identify significant risk factors. A total of 280 male students from 10 secondary schools (both section) of Aden governorate participated in the study, with a mean age of 17.37± 1.42 years. Risk factors associated with substance use included peer pressure (OR=2.34, 95% CI: 1.56-3.42), poor academic performance (OR=1.87, 95% CI: 1.23-2.81), lack of parental supervision (OR=1.62, 95% CI: 1.09-2.37), and low self-esteem (OR=1.45, 95% CI: 1.01-2.11). The findings highlight the complex interplay of social, familial, and individual factors in contributing to substance use among secondary school students. These results can inform targeted interventions and preventive strategies to address the identified risk factors in the community. This study identified several key risk factors for substance use among secondary school students in the community. Understanding and addressing these risk factors is vital for the development of effective preventive interventions and support systems to mitigate the impact of substance use on the health and well-being of young individuals.