IntroductionResearch has demonstrated a robust relationship between psychosocial risk factors (e.g., perceptions of health risk, peer and parent influences, and school climate) and adolescent tobacco use. However, whether internal assets (IAs), factors that promote healthy youth development, can mitigate the adverse effects of psychosocial risks on tobacco use has not been well researched. MethodUsing a population-based sample of middle and high school students (N = 112,364), multilevel logistic and negative binomial regression models estimated the direct effects of cumulative psychosocial risks and IAs on student tobacco use (e.g., combustible, non-combustible, alternative delivery systems) and assessed whether IAs moderated the relationship between psychosocial risks and tobacco use. ResultsResults indicate that every additional psychosocial risk factor was associated with an estimated 100% (AOR: 2.04, 95% CI: 1.88–2.22) to 57% (AOR: 1.57, 95% CI: 1.52–1.62) increase in the odds of using tobacco and a 60% increase in the estimated number of products used. IAs were inversely associated with tobacco use and attenuated the association between cumulative psychosocial risks and use. Among students experiencing all five psychosocial risks, boys had an estimated 20% reduction, and girls an estimated 50% reduction, in the probability of tobacco use at the highest mean scores of IAs. ConclusionUniversal, school-based prevention programs will benefit from identifying and targeting a set of shared risk and protective factors for tobacco use. Bolstering resilience by facilitating students' IAs represents a promising direction for youth focused prevention efforts.