Salmonella enterica serovar Agona is a globally distributed pathogen associated with several hosts, environments and foodborne outbreaks. In this study, we conducted a comprehensive analysis of 4,202 genomes, including an in-depth investigation of 233 French isolates, to elucidate population structure, global dissemination patterns and the genetic determinants underlying ecological adaptation and epidemiological success. Our analyses confirmed the polyphyletic nature of this serotype and identified at least two major genomic lineages differing notably in the presence of fimbrial genes (faeCDE), type VI secretion system (T6SS) gene cluster located in Salmonella pathogenicity island 6 (SPI-6), and SPI-17. The dominant lineage, primarily associated with MLST profile ST13, accounts for approximately 99% of publicly available genomes and exhibits a worldwide distribution across continents, hosts, and ecological niches.The core genome MLST (cgMLST) analysis revealed a major global cluster encompassing 84% of the analyzed genomes, suggesting a common ancestral origin followed by extensive international dissemination. Despite the overall stability of the core genome, Hierarchical Clustering (HC) HC5 analysis uncovered substantial microdiversity within the population, identifying 1,771 distinct clusters. Of these, 1,294 were singletons, while 477 grouped multiple genomes, including several globally distributed clones. Phylogenetic analysis of the 233 French isolates identified 21 well-supported groups linking human infections to poultry, dairy products, environmental sources and imported foods, thereby highlighting complex transmission routes and that a single clone was responsible of the outbreaks occurred in France in 2005 and 2017.Analysis of the accessory genome revealed a broad repertoire of genes associated with tolerance to metals, biocides and antimicrobial compounds, along with the ubiquitous presence of major efflux pump systems, underscoring the strong adaptive capacity of S. Agona to anthropogenic environments. Two Salmonella Genomic Island (SGI)-4-like integrative elements were independently acquired within the French collection and a total of 133 plasmids were predicted, twenty-six of which carried antimicrobial resistance genes. Although our findings suggest that combinations of conserved and accessory determinants (virulence and resistence genes, SGI, plasmids, etc…) contribute to the emergence of clones with epidemic and spread potential. Overall, this study provides new insights into the evolutionary dynamics, ecological versatility and public health relevance of this serotype.