<p>Chronic infections are a persistent global health problem and are frequently sustained by polymicrobial communities rather than by a single pathogen. This review brings together current evidence for the infectome concept, defined as the dynamic set of pathogenic or pathobiont taxa in the host, their shared functional capacities, and the interactions that connect them. We analyze how community-level processes promote persistence, cause diagnostic failure, and drive therapeutic resistance, with emphasis on multispecies biofilms, quorum sensing, horizontal gene transfer, metabolic cooperation, and immune modulation. We also highlight advances in multi-omics and computational integration that now permit high-resolution infectome profiling and reveal taxa and interspecies networks that are not captured by routine culture. Clinical examples such as periodontitis, bacterial vaginosis, chronic rhinosinusitis, device-associated infections, and recurrent urinary tract infections show the translational value of this shift. On the therapeutic side, we discuss infectome-informed options including antivirulence agents, biofilm-disrupting enzymes, bacteriophages and lysins, community-wide susceptibility-guided regimens, and microbiome-restoration strategies. Finally, we identify the main requirements for the field: standardized sampling and analytic workflows, reproducible infectome signatures linked to clinical outcomes, and trial designs able to capture ecological dynamics and meet regulatory expectations for community-targeted interventions. Adopting an infectome perspective can enable precision infectiology and reshape the management of chronic and recurrent infections.</p>