Aim: While the European Union (EU) has approved several COVID-19 vaccines, new variants of concern may be able to escape immunity. The purpose of this study is to project the cost-effectiveness of future lockdown policies in conjunction with a variant-adapted vaccine booster. The exemplary scenario foresees a 25% decline in the vaccine protection against severe disease. Methods: A decision model was constructed using, for example, information on age-specific fatality rates, intensive care unit (ICU) costs and outcomes, and herd protection threshold. The costs and benefits of a future lockdown strategy were determined from a societal viewpoint under three future scenarios—a booster shot’s efficacy of 0%, 50%, and 95%. Results: The cost-effectiveness ratio of a lockdown policy in conjunction with a booster dose with 95% efficacy is €44,214 per life year gained. A lockdown is cost-effective when the probability of approving a booster dose with 95% efficacy is at least 48% (76% when considering uncertainty in input factors). Conclusion: In this exemplary scenario, a future lockdown policy appears to be cost-effective if the probability of approving a variant-adapted vaccine booster with an efficacy of 95% is at least 48%.