In numerous published findings, the cohesion was they have treated sexual experience, suicidal behaviors and depression, as the outcome variables and regard substance use as the core factors. In this study, we aim to do the opposite. We seek to make sense of the linkage by inversing the analytical direction. We intend to examine the association and the likelihood, and observe the levels to which sexual experience, suicidal behaviors, and depression may play a part in the odds of smoking and alcohol drinking among middle school and high school Korean students. The data obtained were cross-sectional from the 2019 Korean Youth Risk Behavior Web-Based Survey, participated by 57, 303 Korean adolescents. Among which are male 52.1%, female 47.9%, ages 15 below 59.2 % and 15 above 40.4%. This study utilized descriptive, Chi-square, and logistic regression analyses. Our basic findings signified that sexual experience and mental health problems doubled the odds of motivation. Chi-square analyses asserted that the association was statistically significant. All variables were notably correlated to substance use at 0.01 level, that is, when sexual experience, suicidal behaviors, and depression tend to increase, there was a high risk of using substances. The results for logistic regression on alcohol drinking, the -2LL statistic is 73157.25, the Cox & Snell R2 is 0.057, and Nagelkerke R2 is 0.078 having the df of 1, with the p value of 0.000l, and the -2LL statistic is 39022.46, the Cox & Snell R2 is 0.064, and Nagelkerke R2 is 0.122 having the df of 1, with the p value of 0.000 for smoking, predicted the maximum likelihood and considerably identified as positive significant indicators in the onset of substance initiation. This study also found that sexual experience had remained robustly substantial with the odds of smoking and drinking, that is, participants with higher sexual experience had the strongest likelihood of substance use motivation. Our overall results contribute to the debate by treating sexual experience, suicidal behaviors, and depression as precedent significant risk factors for developing substance use behaviors among Korean adolescents. For efficient and effective management of sexual experience, suicidal behaviors and depression on teenagers, findings underscore the need for early detection on adolescents at risk. A comprehensive prevention and protective efforts is required along with continuous parental guidance. Intervention programs with coping skills to handle emotional and behavioral problems is essential to help reduce the probability of an increased risk factors and subsequently lessen the threat for developing cigarette smoking and alcohol drinking behaviors among teenagers. School-based programs that can create synergy by embedding teenagers in an academic environment that is equally supportive, beneficial and can help promote a positive mindset is recommended.