<p>Increases in levels of heavy metals and microplastics attributed to increasing population, urbanization, industrialization, and changing lifestyle have put immense pressure on riverine ecosystems by causing severe ecological, environmental, and human health risks. This study provides a comprehensive understanding of the distribution, sources, impacts, case studies, and mitigative measures to combat heavy metal and microplastic contamination of rivers. Heavy metals demonstrate bioaccumulation and biomagnification in aquatic food webs, leading to genetic, physiological, and reproductive disruptions in aquatic organisms. Microplastics have the potential to disturb food webs by modifying the nutrient cycles and habitats, which influence the species interactions and impact community structure. This study also highlights the seasonal and spatial dynamics of heavy metals and microplastics contamination, pollutant transfer to aquatic organisms, and resulting ecological ramifications, including oxidative stress, genetic damage, and physiological dysfunctions in freshwater species. The transfer of contaminants from river water and sediments into the aquatic food chain results in bioaccumulation and biomagnification, thereby elevating ecological risks and raising concerns for human health through trophic exposure. Strategies for sustainable river management, enhanced river water quality monitoring, and global regulatory frameworks are critically detailed to address the issue by highlighting the need for stringent policies to mitigate pollutant impacts. Additionally, the study formulates the policy recommendations to protect the health of the river ecosystem and communities that depend on the river ecosystem.</p> Graphical Abstract <p></p>