Background: Pneumococcal disease (PD) is a major cause of morbidity and mortality in young children in Asia and globally. Pneumococcal conjugate vaccines (PCVs) have significantly reduced the burden of PD when included in pediatric national immunization programs (NIPs). This study estimates the clinical and economic burden of PD due to serotypes contained in different PCVs in children aged < 5 years in eight Asian countries/territories. Methods: Based on published data, a cohort-based decision analytic model was used to estimate annual PD cases, deaths, and direct medical costs associated with serotypes contained in PCV10, PCV13, PCV15, and PCV20. Results: PD incidence rates were lower in regions with PCV13 in their NIP than those without. Serotypes contained in higher but not lower valency PCVs resulted in a significant incremental clinical and economic burden, although the difference between PCV13 and PCV15 serotypes was generally small. Moving from PCV13 to PCV20 was estimated to result in greater clinical and economic burden reductions. Conclusions: This study demonstrates the remaining and incremental burden of PD from PCV10 to PCV20 serotypes in young children in selected Asian regions. Extending NIP access to higher-valency PCVs with broader serotype coverage and improving vaccine uptake will help prevent morbidity and deaths and save healthcare costs.