<p>Polyolefin hydrocracking represents a promising route for upcycling plastic waste, but achieving efficient depolymerization requires a new generation of bifunctional nanocatalysts. In this Review we revisit the conceptual framework of traditional hydrocarbon hydrocracking strategies and re-examine their relevance to the emerging field of polymer catalysis. We demonstrate that the established nanoscale structure–activity relationships provide a valuable foundation for understanding polyolefin hydrocracking. The macromolecular nature of plastics—with its associated mass transport limitations, distinct impurity profiles and unique interactions at the catalyst–polymer nano-interface—partially disrupts their direct transferability. This breakdown creates new opportunities to engineer catalysts with hierarchical nanoarchitectures that maximize active site accessibility and impurity tolerance. Finally, we highlight the urgent need to integrate nanoscale catalytic insights with reactor-scale engineering and standardized evaluation protocols to ensure reproducibility and scalability. By bridging these fields, a new nanoscience for plastic valorization can be established to support a circular economy.</p>