Hypervirulent Klebsiella pneumoniae (hvKp) causes invasive infections and severe systemic inflammation. In this study, outer membrane vesicles (OMVs) derived from clinically isolated hvKp and classical K. pneumoniae (cKp) strains were characterized using an integrated proteogenomic workflow combining whole-genome sequencing and label-free LC–MS/MS proteomics. The dataset includes quantitative proteomic profiles of OMVs and whole-cell lysates together with strain-specific protein annotations for comparative analyses of OMVs cargo composition, functional annotation, and pathogenicity.