Purpose: Drug use during adolescence can have lasting health consequences, and understanding the factors that contribute to drug use is essential for effective prevention. This study aimed to identify the factors influencing habitual drug use among South Korean adolescents. It employed Bronfenbrenner's ecological model to examine personal, familial, school-related, and social factors. Methods: The study analyzed data from the 19th Korea Youth Risk Behavior Survey for 41,928 students from 1st grade of middle school to 3rd grade of high school. Data analysis involved cross-tabulation and logistic regression for complex samples. Results: The prevalence of habitual drug use was 1.4%. Significant personal factors included smoking [adjusted odds ratio (aOR) = 2.61], alcohol consumption (aOR = 1.55), sexual intercourse (aOR = 1.45), smartphone overdependence (high-risk group aOR = 2.04, potential risk group aOR = 1.31), suicidal ideation (aOR = 2.66), depressed mood (aOR = 1.87), and loneliness (aOR = 1.88). Significant family factors included non-cohabitation with family (aOR = 1.86) and both parents being foreign-born (aOR = 3.36). Experience of violence (aOR = 2.95) was also a significant factor. Conclusion: This study highlights the need for an integrated approach to prevent adolescent drug use by addressing adolescents' personal behaviors, family dynamics, and school environments. Prevention programs should account for the influence of multiple systems on habitual drug use. School and community nurses should adopt a comprehensive, multi-dimensional strategy that involves families, schools, and communities to prevent adolescent drug use. Additionally, there is a need to develop family- centered and culturally sensitive drug prevention programs for adolescents. (c) 2025 Korean Society of Nursing Science. Published by Elsevier BV. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).