Over 50% of aquatic food production depends on aquaculture, which faces sustainability challenges, including wastewater pollution, eutrophication from excess nitrogen and phosphorus, and antimicrobial resistance (AMR) and antibiotic resistance genes (ARGs) from effluent discharge. Conventional wastewater treatment can’t fully address these problems, increasing environmental and health risks. The concept of precision microbiome engineering (PME), which includes next-generation probiotics, synthetic microbial communities (SynComs), and omics-guided bioremediation consortia, is seen as revolutionary because it can enhance bioremediation and prevent antimicrobial resistance (AMR). However, PME’s application to host-associated and environmental microbiomes is less studied. This review proposes a strategy linking host microbiome manipulation to wastewater bioremediation to address AMR. It combines environmental biotechnology and aquaculture science to evaluate the role of PME across these interconnected domains critically. It provides a comprehensive overview of the microbial ecology of host systems in aquaculture and their corresponding effluents. The text analyzes how probiotics, postbiotics, and synbiotics boost fish immunity and combat resistant pathogens. It also assesses advanced bioremediation methods like biofloc, MBBRs, and microbial consortia. This review redefines PME as an integrated system rather than isolated interventions, considering current knowledge on aquaculture wastewater, AMR mechanisms, and treatment limitations. It critically assesses ecological, regulatory, biosafety, and scalability issues, highlighting knowledge gaps and dangers. The article proposes a model combining SynCom construction using multi-omics, CRISPR, and real-time microbiome monitoring via AI.