Background: Streptococcus pneumoniae Serotype 3 (SPN3) remains a significant cause of morbidity and mortality worldwide despite of pneumococcal conjugate vaccine (PCV) implementation. We explored genomic profile of SPN3 from children and adult groups to understand population structure and evolution dynamics of SPN3 in Indonesia. Methods: We undertook whole genome sequencing (WGS) from 19 isolates of SPN3 in Indonesia between 2017 and 2021 prior to PCV introduction. This study assessed sequence types (STs), global pneumococcal sequence cluster (GPSC), genome prediction of antimicrobial resistance (AMR) profile, pangenome analysis, phylogenetic tree, and genome comparative of capsular polysaccharide (cps) locus. Results: We identified ST451-GPSC234 (n = 5) and ST180-GPSC12 (n = 4), ST458-GPSC51 (n = 2), ST3805-GPSC12 (n = 2), ST4909-GPSC363 (n = 2), ST700-GPSC10 (n = 1), ST5292-GPSC309 (n = 1), ST505-GPSC12 (n = 1), and ST4233 (n = 1). Genome prediction of AMR discover isolates were resistant to tetracycline (n = 5); co-resistant of chloramphenicol and tetracycline (n = 2); co-trimoxazole and tetracycline (n = 1). We observed SPN3 possess closed pangenome characteristic, indicates more stable genetic repertoire. We found 5 absent genes in cps locus including cpsABCD and tnp in ST700-GPSC10 lineage. Conclusions: SPN3 has potential genomic profile to enhance the ability of this strain to endure selective pressure such as PCV introduction. © 2025