<p>Antimicrobial resistance (AMR) and heavy metal resistance (HMR) in aquatic ecosystems are increasing global health concerns driven by anthropogenic pollution of water systems. Municipal wastewater, hospital effluents, industrial discharge, agricultural runoff, and aquaculture activities contribute to the persistence and dissemination of resistant microorganisms and resistance genes in aquatic environments. Clinically important waterborne pathogens, including <i>Escherichia coli</i>, <i>Salmonella Typhi</i>, <i>Shigella</i> spp., and <i>Vibrio cholerae</i>, readily acquire resistance under continuous environmental stress conditions. Heavy metals further enhance AMR persistence through co-selection and cross-resistance mediated by mobile genetic elements carrying both antimicrobial and heavy metal resistance genes. This review summarizes the major environmental drivers, molecular mechanisms, and dissemination pathways associated with AMR–HMR interactions in aquatic systems. Recent advances in wastewater-based epidemiology, metagenomic surveillance, and resistance monitoring are highlighted as emerging tools for environmental and public health assessment. Current mitigation approaches, including advanced oxidation processes, membrane bioreactors, nanomaterial-based filtration, and microbial bioremediation, are also evaluated. A multidisciplinary One Health framework is essential for limiting environmental resistance dissemination and protecting human, animal, and ecosystem health.</p> Graphical abstract <p>Heavy metal-driven co-selection of antimicrobial resistance and monitoring strategies in aquatic environments. Created with BioRender.com.</p> <p></p>