Significance To aid in prioritizing the development of tuberculosis (TB) vaccines most likely to reach the 2050 TB elimination goal, we estimated the impact and cost-effectiveness of a range of vaccine profiles in low- and middle-income countries. Using mathematical modeling, we show that vaccines targeted at adolescents/adults could have a much greater impact on the TB burden over a 2024–2050 time horizon than those vaccines targeted at infants. Such vaccines could also be cost-effective, even with relatively high vaccine prices. Our results suggest that to achieve the 2050 elimination goals, future TB vaccine development should focus on vaccines targeted at adolescents/adults, even if only relatively low efficacies and short durations of protection are technically feasible. To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40–80% efficacy, and to be targeted at “infants” or “adolescents/adults.” Vaccine prices were tiered by income group (US $1.50–$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024–2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11–24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42–1.58) million TB cases could be prevented at $1,692 ($634–$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle–, and upper-middle–income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.