Objective To analyze the drug resistance and genomic characteristics of clinically isolated hypermucoviscous Klebsiella pneumoniae (hmKp). Methods Klebsiella pneumoniae isolated from clinical specimens from the sentinel hospitals of National Pathogen Identification Network in Huai’an City from 2019 to 2023 were collected, strains were identified by VITEK 2 Compact, mucus phenotype was determined by string test, resistance of hmKp was determined by microbroth dilution method. Molecular typing was conducted by whole-genome sequencing technology, annotation of virulence and resistance genes carried by strains was performed. Results A total of 60 strains of hmKp were collected, mainly isolated from sputum specimens (33.33%) and blood specimens (28.33%). The average genome size of 60 strains was 5.6 Mb, with an average GC content of 57.09%. Multilocus sequence typing (MLST) showed that there were 28 ST types, with the dominant ST types being ST11 (11.67%), ST15 (11.67%), and ST412 (10.00%). Core genome MLST (cgMLST) analysis revealed that some strains were highly homologous, and no outbreak strains were found. Multidrug-resistant strains accounted for 60.00%, while imipe-nem-resistant strains accounted for 28.33%. 64 types of resistance genes were carried, 84.38% of which were located on mobile element. The carriage rates of fosfomycin-related resistance genes and extended-spectrum β-lactam antibiotic-related resistance genes were relatively high in the strains, at 100% and 98.33%, respectively. Among carbapenem-resistance gene bla_KPC-2, 21.67% was carried by ST11, ST1, and ST15 strains, among bla_NDM-5 gene, 3.33% was carried by ST76 strain. A total of 101 virulence genes were carried, most were Colibactin and type Ⅵ secretion system-related virulence genes. All strains carried capsule synthesis regulation-related genes (rcsA, rcsB), efflux pump-related genes (acrA, acrB), and enterobacterin-related genes (entABCEF, fepABCDFG, fes). Conclusion Clinically isolated hmKp in Huai’an exhibits multidrug resistance, with dominant ST types ST11, ST15, and ST412, carrying multiple horizontally transferable resistance and virulence genes, prevention and control measures should be strengthened.