Nuclear power provides a chance for the decarbonization of global energyrelated emissions. However, the spent fuel produced by nuclear reactors contains various radionuclides, which require further disposal and treatment. Therefore, the enrichment and separation of radionuclides are of great significance for the recycling and utilization of resources. Organic polymer materials have attracted great attention due to their excellent physicochemical properties of rapid kinetics, high adsorption capacity, high selectivity, and diverse functionalization. This review provides an overview of the use of pristine polymers, functionalized polymers, and polymer-based composites for the highly efficient enrichment and separation of different kinds of radionuclides (i.e., U, Tc, I). The synthesis strategy, radionuclides enrichment and separation ability, and related mechanism are comprehensively summarized. The structure−property relationships in polymer-based materials that underpin their outstanding environmental remediation performance are also illustrated. Finally, the challenges and perspectives of polymer-based materials for future radionuclide separation and legacy nuclear waste management are reasonably proposed, aiming to design functional polymers for task-specific applications.