Multiple factors, including marijuana decriminalization/legalization, tobacco endgame discourse, and alcohol industry pressures, suggest that the retail regulatory environment for psychoactive or addictive substances is a dynamic one in which new options may be considered. In most countries, the regulation of tobacco, marijuana, and alcohol is neither coherent, nor integrated, nor proportional to the potential harms caused by these substances. We review the possible consequences of restricting tobacco sales to outlets run by government-operated alcohol retail monopolies, as well as the likely obstacles to such a policy. Such a move would allow governments more options for regulating tobacco sales, and increase coherence, integration, and proportionality of substance regulation. It might also serve as an incremental step toward an endgame goal of eliminating sales of commercial combustible tobacco.