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Microplastics have become a ubiquitous environmental contaminant in natural waters, raising significant concerns regarding aquatic ecosystem health and potential human exposure. A comprehensive synthesis of current knowledge on microplastic pollution in freshwater and marine systems is presented, focusing on sources, distribution patterns, environmental behavior, and associated risks. In freshwater environments, microplastic inputs are closely linked to human activities and land use, with wastewater treatment plant effluent, urban runoff, and agricultural drainage serving as major pathways. In marine systems, microplastics undergo dynamic transport influenced by particle properties, hydrodynamic conditions, and biological interactions such as biofouling and aggregation, leading to widespread distribution from coastal zones to deep sea sediments. Importantly, the role of the freshwater–estuarine–marine continuum is emphasized, highlighting the coupled processes of transport, retention, and remobilisation that govern the spatiotemporal distribution and ultimate fate of microplastics across interconnected aquatic systems. Toxicological effects on aquatic organisms are further examined, particularly immunotoxicity and neurotoxicity, alongside potential human health risks via ingestion, inhalation, and dermal exposure. Attention is drawn to the discrepancy between experimental exposure conditions and environmentally relevant concentrations, which constrains robust risk assessment. Current mitigation strategies, including source reduction, wastewater treatment upgrades, transport interception, and degradation technologies, are critically evaluated in terms of effectiveness and limitations. A clear distinction is made between apparent removal and actual degradation, with further consideration of the environmental implications associated with sludge retention and degradation byproducts. Finally, key research priorities are identified, including the need for standardized detection methods, improved exposure assessment, development of environmentally benign alternatives, and strengthened policy-driven source control. These insights provide a basis for advancing sustainable management strategies for microplastic pollution in natural waters.