Abstract Health-care-associated infections (HAIs) are a global threat. Microbial whole-genome sequencing (WGS) can strengthen HAI prevention strategies by enabling high-resolution detection and tracking of pathogen transmission and predicting clinically relevant phenotypic traits, such as antibiotic resistance and virulence. Although WGS continues to serve as a vital adjunct in outbreak responses, its role has evolved to include prospective pathogen surveillance and epidemiological monitoring.