In aquatic environments, microplastics, defined as polymeric particles smaller than 5 mm, have become persistent and biologically active contaminants that have a variety of effects on fish physiology, immunology, and general health. The health of fish and the overall balance of aquatic ecosystems are severely threatened by their increasing presence. Their broad dispersion throughout trophic levels is made possible by both primary sources (industrial microbeads and synthetic fibres) and secondary degradation of larger polymers. MPs accumulate in vital tissues such as the stomach, liver, gills, and muscle after entering fish by ingestion, gill uptake, or skin contact. Once ingested, MPs cause a series of physiological disruptions that affect development, reproduction, and energy balance. These disruptions include oxidative stress, lipid peroxidation, mitochondrial malfunction, and metabolic relocation. By changing cytokine profiles, lowering lysozyme and phagocytic activity, and weakening mucosal defences, MPs interfere with both innate and adaptive immune responses. These immunological disruptions increase disease susceptibility and alter host-pathogen interactions; they are often made worse by related pollutants and biofilm invasion. MPs dysregulate genes associated with inflammation, apoptosis, and detoxification, according to molecular investigations using transcriptomic, proteomic, and metabolomic techniques, offering mechanistic insights into their sublethal toxicity. Because MPs are found in edible fish tissues, they act as ecological vectors for pollutants and diseases, spreading their effects through aquatic food webs and posing serious risks to food safety. In the context of sustainable fisheries and aquacultureAquaculture management, this chapter offers a thorough synthesis of the most recent research on MP-induced physiological and immunological changes in fish, with a focus on mechanistic pathways, biomarker applications, ecological implications, and mitigation techniques.