Purpose. This study examines smoking and alcohol use among disadvantaged Hill tribe adolescents (12–19 years old) in northern Thailand. We use Leininger’s theory to better understand how cultural norms, health literacy, and perceived impacts influence these behaviors. Methods. The study utilized a cross‐sectional approach and involved 324 participants. Data were collected using standardized questionnaires (Thai‐AUDIT, FTND) to assess substance use and health literacy. Focus group discussions provided further insights into cultural norms and the impacts of such behaviors. Results. Over half (51.2%) of participants reported ever consuming alcohol, and 20.10% currently smoke cigarettes. Health literacy levels were adequate across all subgroups. Multiple regression analyses with a hierarchical approach identified the cultural and social factors including age at first drinking (β = −0.34, t = −2.68, p = 0.01) and factors related to the impact of past usage (impact on one’s health: β = −0.33, t = −2.48, p = 0.01, and impact on deep feelings: β = −0.33, t = −2.33, p = 0.02), which accounted for 18.2% of the variance in current alcohol consumption frequency (adjusted R2 = 0.182, F = 3.04, p = 0.01). The analysis revealed that there was no statistically significant relationship between age at first smoking and the current amount of cigarettes (β = −0.01, p = 0.15). As expected, health literacy was shown as the only predictor that significantly predicted the current amount of cigarettes (β = −0.40, p = 0.003), accounting for 14.1% of the current amount of cigarettes (adjusted R2 = 0.141, F = 4.08, p = 0.05). Conclusion. The results provide further evidence that the standard intervention is not appropriate for utilization with this specific group. Therefore, we propose a multifaceted culturally appropriate approach that integrates the insights derived from the focus group discussion while currently targeting health literacy, alcohol attitudes, and early substance use prevention through family and community awareness initiatives.