The relationship between river hydrology and microplastic (MP) pollution is complex: increased discharge does not always mobilize more MPs, but floods can effectively flush out MPs from river catchments. Climate change and water resource management further influence MP pollution and its fate by altering river hydro-sedimentary regimes. This review investigates the interconnected impacts of these factors from a comprehensive perspective, focusing on how they affect MP concentration in freshwater ecosystems, particularly in regulated rivers and associated reservoirs. Our review reveals a scarcity of studies that jointly analyze the interrelated issues of MP pollution, water resource management, and climate change. Key findings indicate that variations in river discharge significantly influence MP mobilization, mainly depending on catchment land use, channel morphology, position within the catchment, and MP characteristics. Reservoirs function as both sinks and sources of MPs, underscoring their complex role in MP dynamics and the need for sustainable sediment management strategies. The increasing frequency of extreme weather events, driven by climate change, along with prolonged droughts intensified by water management practices, exacerbates MP pollution. These changes contribute to the local concentration of MPs, posing direct physical threats to aquatic organisms, particularly benthic species, through pollution and habitat alterations. Current policies on plastic pollution, water resources and climate change are underdeveloped, as these topics have been treated separately so far. In conclusion, this review provides perspectives on future research and policy directions to address challenges posed by MPs and to preserve rivers against multiple stressors.