Group A Streptococcus causes a wide range of diseases from relatively mild infections including pharyngitis to more severe illnesses such as invasive diseases and rheumatic heart disease (RHD). Our aim is to estimate the cost-effectiveness of a hypothetical Strep A vaccine on multiple disease manifestations at the global-level. Cost-effectiveness analyses were carried out by building on the potential epidemiological impact of vaccines that align with the WHO's Preferred Product Characteristics for Strep A vaccines. Maximum vaccination costs for a cost-effective vaccination strategy were estimated at the thresholds of 1XGDP per capita and health opportunity costs. The maximum cost per fully vaccinated person for Strep A vaccination to be cost-effective was $385-$489 in high-income countries, $213-$312 in upper-income-income countries, $74-$132 in lower-middle-income countries, and $37-$69 in low-income countries for routine vaccination at birth and 5 years of age respectively. While the threshold costs are sensitive to vaccine characteristics such as efficacy, and waning immunity, a cost-effective Strep A vaccine will lower morbidity and mortality burden in all income settings.