Spent nuclear fuel (SNF) contains highly radioactive products with half-lives ranging from days to millions of years, posing significant risks to human health and the environment. Conventional recovery of uranium and plutonium from SNF is achieved using the PUREX (Plutonium–Uranium Extraction) process, which employs tri-n-butyl phosphate (TBP) in kerosene or n-dodecane as a diluent. While effective in extracting UO₂²⁺ and Pu⁴⁺ for conversion to UO₂ and PuO₂, the process generates raffinates containing other valuable fission products. Conventional organic solvents used in these extraction processes are volatile, toxic, flammable, and prone to radiolytic and thermal degradation, creating operational and environmental hazards. Consequently, research has focused on identifying safer alternative solvents. Ionic liquids (ILs) have emerged as promising candidates due to their negligible vapor pressures, non-flammability, high thermal and radiological stability, and tunable solvent properties. This study reviews recent advances in computational and experimental screening of solvents for SNF reprocessing, emphasizing the potential of ILs to serve as environmentally benign, efficient, and stable alternatives to conventional extraction solvents. Adoption of such advanced solvent systems could significantly improve the safety, sustainability, and efficiency of nuclear fuel reprocessing operations.