This study sought to assess the cost-effectiveness of population-based tobacco control interventions, which included health promotion and education, smoke-free models, cessation programs, warning on package, marketing bans, and raising tax. Standardized activity-based costing ingredient approach was applied with the provider perspective to calculate interventions cost from 2013 to 2017. The potential health impacts of the aforementioned interventions were calculated through a Microsoft Excel-based modeling adapted from Higashi et al and Ngalesoni et al. All six population-based tobacco control interventions were highly cost-effective with ranges from 1405 VND (Vietnamese Dong) to 135 560 VND per DALY (disability-adjusted life year) averted. It was identified that raising cigarette taxes and applying health warnings on tobacco packages are the most favorable, cost-effective interventions. The results from this study provide a robust message that calls for increased attention and efforts in developing an appropriate policy agenda, which jointly integrates both political and community-based interventions, to maximize intervention impact on tobacco use.