Purpose: The aim of this study was to construct a structural equation model that would further explain the continuously increasing substance use disorder in Korean adolescents. Methods: Survey visits using a structured questionnaire were conducted with 3,885 students in 2 middle schools and 2 high schools in Busan. A total of 13 instruments were used in this model. The analysis of data was done with both SPSS 14.0 for descriptive statistics and AMOS 5.0 for covariance structure analysis. Results: Based on the constructed model, belief on substance use was found to have a significantly direct effect in influencing adolescent substance use. In addition, other factors such as family environment, satisfaction with school life, self-concept, social support, and personality vulnerability indirectly affected substance use. The final modified model yielded Chi-square=2,987(p<.001), df=121, ${chi}^2$/df=22.1, GFI=.96, AGFI=.93, NFI=.91, PNFI=.72, PGFI=.72, RMSEA=.07 and exhibited fit indices. Conclusion: This study constructed a model that addresses the factors related to adolescent substance use and explains the relationship of these factors in influencing substance use among Korean adolescents. Findings from this study can contribute to designing appropriate prevention strategies to reduce substance related disorders in adolescents.