Microplastics (MPs) are widespread pollutants in freshwater aquaculture systems, entering through the degradation of pond linings and nets, contaminated aquafeeds, agricultural runoff and atmospheric deposition. Nile tilapia (Oreochromis niloticus) an omnivorous and intensively farmed fish, is heavily exposed to MPs however, the interaction between MPs, gut microbiota and mucosal immunity in this species has not been comprehensively assessed. In this review, we summarize recent evidence on the sources, uptake and accumulation of MPs and on how MP exposure causes gut dysbiosis, characterized by decreased alpha diversity, increased abundance of Proteobacteria and reduced levels of beneficial Firmicutes and Fusobacteria, which may affect short chain fatty acid biosynthesis. We then examine how dysbiosis and barrier dysfunction are linked to activation of the TLR4/MyD88/NF-κB, MAPK, JAK/STAT, Nrf2/Keap1 and NLRP3 inflammasome pathways and to oxidative and histopathological damage in the intestine and liver. Special attention is given to age dependent susceptibility, as juvenile fish show dysregulated inflammatory genes under conditions in which no effects are observed in adults. Candidate molecular, biochemical, hematological and non-invasive mucus-based biomarkers are discussed alongside the feasibility of multi omics approaches (metagenomics, transcriptomics, proteomics and metabolomics) for resolving host microbiota environment interactions. Mitigation strategies, including multi species probiotics, algal supplements, engineered biochar, feed management and biodegradable materials, are also evaluated. Key knowledge gaps remain in chronic low dose exposure, mixture effects, nanoplastics, reversibility of dysbiosis and methodological standardization. Addressing these gaps will be essential for developing resilient and sustainable tilapia aquaculture.