ACKR5 and infection: The considerable overlap in virulence genes, AMR genes, and plasmid transfer gene profiles between human isolates and those from other sources implies potential links between foodborne contamination and human infections.<h4>Importance</h4>This study provides a comprehensive genomic analysis of over 15,000 <i>Salmonella</i> Infantis isolates, revealing widespread antimicrobial resistance (AMR), virulence gene prevalence, and plasmid transfer potential.