Description: Objective The community of residence (ie, urban vs rural) is one of the known factors of influence on substance use and misuse (SUM). The aim of this study was to explore the community-specific prevalence of SUM and the associations that exist between scholastic, familial, sports and sociodemographic factors with SUM in adolescents from Bosnia and Herzegovina. Methods In this cross-sectional study, which was completed between November and December 2014, the participants were 957 adolescents (aged 17 to 18 years) from Bosnia and Herzegovina (485; 50.6% females). The independent variables were sociodemographic, academic, sport and familial factors. The dependent variables consisted of questions on cigarette smoking and alcohol consumption. We have calculated differences between groups of participants (gender, community), while the logistic regressions were applied to define associations between the independent and dependent variables. Results In the urban community, cigarette smoking is more prevalent in girls (OR=2.05; 95% CI 1.27 to 3.35), while harmful drinking is more prevalent in boys (OR=2.07; 95% CI 1.59 to 2.73). When data are weighted by gender and community, harmful drinking is more prevalent in urban boys (OR=1.97; 95% CI 1.31 to 2.95), cigarette smoking is more frequent in rural boys (OR=1.61; 95% CI 1.04 to 2.39), and urban girls misuse substances to a greater extent than rural girls (OR=1.70; 95% CI 1.16 to 2.51,OR=2.85; 95% CI 1.88 to 4.31,OR=2.78; 95% CI 1.67 to 4.61 for cigarette smoking, harmful drinking and simultaneous smoking-drinking, respectively). Academic failure is strongly associated with a higher likelihood of SUM. The associations between parental factors and SUM are more evident in urban youth. Sports factors are specifically correlated with SUM for urban girls. Conclusions Living in an urban environment should be considered as a higher risk factor for SUM in girls. Parental variables are more strongly associated with SUM among urban youth, most probably because of the higher parental involvement in children’ personal lives in urban communities (ie, college plans, for example). Specific indicators should be monitored in the prevention of SUM.