Background The measles-mumps-rubella (MMR) trivalent vaccine constitutes a cornerstone in controlling mumps incidence. However, variations in vaccination timing coupled with the gradual waning of vaccine-induced immunity have contributed to an increase in mumps cases among adolescents, alongside dynamic shifts in age distribution. This study aims to elucidate the optimal vaccination strategies for both the general population and age-specific cohorts through a comprehensive, multidimensional evaluation. Methods: We systematically collected and integrated global annual average mumps incidence data (2000–2023) from 23 countries and immunization schedule databases to construct 16 hypothetical vaccination strategies, including the baseline regimen (a single dose administered at 18–24 months), an improved timing regimen (an additional primary dose at 8–9 months before 24 months), and booster regimens (one to two supplementary doses during childhood or adolescence). We developed an individual-based disease transmission model (IBM) incorporating real-time vaccination, age growth, and age-specific contact frequency and preference, driven by estimated time-varying reproduction numbers, to simulate the impact of different strategies after five years of steady-state implementation on cumulative case counts, overall infection numbers, outbreak magnitude, and age-specific infection risks. This comprehensive evaluation framework enables us to assess the impact of dosing and vaccination timing on the immunological control of mumps. Findings: For overall population control, a strategy entailing a single vaccine dose at 18–24 months, a booster at 13–14 years, and another at 18–19 years yielded optimal results, achieving a reduction of 99.79% in both cumulative infections and cases over the subsequent five years. When implementing immunization exclusively before 24 months, a dual-dose primary regimen reduced cumulative infections and cases by an additional 4.79% and 4.91% over the subsequent five years, respectively, compared to a single-dose approach. Moreover, within identical booster vaccination age groups, completing a dual-dose primary immunization before 24 months generally provided superior protection relative to the single-dose protocol. Age-specific analyses further revealed that while the dual-dose strategy before 24 months lowered the proportion of cases and infections in the 0–4 year age group compared to the single-dose regimen, the absolute numbers remained largely unchanged; under the same primary immunization framework, delaying the administration of the final dose decreased the infection proportion in the 20–25 year age group, with a dual-dose booster implemented after age 2 effectively minimizing the proportion of cases among individuals over 20. Notably, administering the booster at ages 13–14 years consistently suppressed the primary infection peak observed in individuals aged 10–14 years, reducing infection numbers by more than 99.00%. Interpretation： A phased immunization strategy that integrates primary vaccination with sequential booster doses may help reduce the transmission of mumps in our simulations. Model projections suggest that prioritizing booster vaccinations during adolescence could lower infection risks among vulnerable age groups and may provide additional protection for women of reproductive age.
