Mathematical modeling indicates that next-generation tuberculosis vaccines demonstrating efficacy against asymptomatic TB infections could prevent millions of deaths globally by 2050. The analysis examined vaccines currently in Phase III trials, projecting that even modest protection against subclinical disease could yield outsized public health benefits compared to vaccines targeting only active tuberculosis cases. This finding challenges conventional vaccine development priorities that focus primarily on preventing symptomatic disease. Asymptomatic TB infections represent a massive reservoir of transmission, with infected individuals often unaware they harbor and can spread the pathogen. Breaking this silent transmission chain represents a paradigm shift in TB control strategy. The modeling suggests vaccines achieving 50% efficacy against subclinical infection could prevent up to 8.5 million deaths over 25 years. However, the projections rely heavily on assumptions about transmission dynamics and vaccine uptake in high-burden regions. Current late-stage TB vaccine candidates show varying degrees of protection against different infection states, making real-world efficacy against asymptomatic disease a critical unknown. If validated in clinical practice, such vaccines could revolutionize TB elimination efforts by targeting the disease's hidden transmission networks.