Salmonella enterica remains a major threat to animal and human health because of its broad host range, increasing antimicrobial resistance (AMR), and capacity to form biofilms. Biofilm formation enhances bacterial persistence in host tissues, farm environments, food-processing systems, and clinical reservoirs, while also contributing to their tolerance against antibiotics, disinfectants, and other stresses. However, biofilm capacity is not uniform across serovars and is influenced by host adaptation, niche specialization, and accessory genome content. This review synthesizes current knowledge on the relationship between biofilm formation, AMR, and serovar-specific adaptation in Salmonella. It examines biofilm-associated traits across various hosts (e.g., gastrointestinal tract and gallbladder, and environmental (e.g., food-production and clinical) niches, and discusses comparative evidence from genomic, transcriptomic, proteomic, and metabolomic studies. Particular attention is given to the emerging concept of comparative biofilmomics, which integrates phenotypic and multi-omics data across diverse serovars and host sources to identify conserved and niche-specific determinants of persistence. This framework may help define high-risk lineages that couple multidrug resistance (MDR) with enhanced biofilm-forming capacity. A better understanding of these linked traits will support the development of more targeted interventions for controlling persistent Salmonella in veterinary, food production, and public health settings.