Effective control of bacterial infections remains a significant challenge in aquaculture. The marine bacterium (), responsible for piscirickettsiosis, causes widespread infections in various salmon species, leading to substantial mortality and economic losses. Despite efforts to genetically characterize , critical gaps persist in understanding its virulence factors, antimicrobial resistance genes, and single-nucleotide polymorphisms (SNPs). This study addresses these gaps through a comparative analysis of the pan-genome and core genomes of 80 strains from different geographical regions and genogroups. had an open pan-genome consisting of 14,564 genes, with a core genome of 1257 conserved genes. Eleven virulence-related genes were identified in the pan-genome, categorized into five functional groups, providing new insights into the pathogenicity of . Unique SNPs were detected in four key genes (, , , and ), serving as robust molecular markers for distinguishing the LF and EM genogroups. Notably, AMR genes identified in four LF strains suggest evolutionary adaptations under selective pressure. Functional annotation of the core genomes using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases demonstrated conserved gene clusters linked to essential intracellular survival mechanisms and bacterial pathogenicity. These findings suggest a direct association between core genome features and variations in pathogenesis and host-pathogen interactions across genogroups. Phylogenetic reconstruction further highlighted the influence of AMR genes on strain divergence. Collectively, this study enhances the genomic understanding of and lays the groundwork for improved diagnostic tools and targeted therapeutics to manage piscirickettsiosis in aquaculture.