Abstract: The aquaculture industry currently faces significant challenges due to the coexistence of environmental pollution and pathogenic bacterial diseases. Environmental pollutants not only directly harm cultured organisms but also drive the evolution of bacterial virulence, thereby increasing the risk of disease outbreaks and complicating prevention and control efforts. A systematic understanding of this interaction mechanism is crucial for formulating effective health management strategies in aquaculture. This review focuses on the sources and distribution of environmental pollutants such as microplastics, heavy metals, pesticides, antibiotics, and persistent organic pollutants (POPs) within aquaculture systems. It summarizes the epidemiological characteristics and pathogenic mechanisms of key bacterial pathogens, including Vibrio spp. and Aeromonas spp.. Furthermore, from a practical environmental perspective, the review synthesizes the mechanisms by which various pollutants, individually or in combination, synergize with pathogens to exacerbate toxic effects on aquaculture organisms. These mechanisms include compromising host immunity, acting as selective pressures for virulence evolution, and disrupting microbial ecological balance. Finally, integrating multi-scale perspectives-from molecular and cellular to individual levels-and leveraging multi-omics technologies, future research directions are proposed to deepen the understanding of the tripartite interaction network among “pollutants-pathogens-host”.