UPCYCLE aims to demonstrate novel circular value chains that transform currently non-recyclable mixed plastic waste into biodegradable and recyclable materials for packaging applications. Building on the promising results of the H2020 UPLIFT project, UPCYCLE addresses specific scalability hotspots to reach economic viability. The project scales up its novel plastic biorefinery and ecopolymers with a strategy that leverages: (1) A Safe-and-Sustainable-by-Design framework to ensure safety (i.e., non-toxic materials), a reduction in GHG emissions (-30%), and economic viability (<40% selling price); (2) AI-powered fast-track innovation for process intensification; (3) A versatile biorefinery process to valorise mixed plastic waste (both fossil- and bio-based) and secondary biomass residues; (4) A smart polymerisation and formulation strategy using bio-based, degradable additives to tune biodegradability and enhance technical performance for four selected packaging use cases. Leveraging a multidisciplinary consortium of top-tier academic institutions and industry leaders, UPCYCLE is poised to create significant impact in the packaging industry. UPCYCLE’s ecopolymers, derived from plastic and biomass waste streams, promote a viable circular business model for European recyclers, polymer processors, compounders, and packaging producers. Moreover, our strategy demonstrates how renewable and upcycled building blocks and additives can be blended into commercially available polymers to delivers novel PHA-, PLA- and Furan-based packaging formulations, to successfully modulate degradability and technical performance, based on the application. By providing the tools to improve properties and economic viability of polymers systems that are already in the market, we provide a fast-track pathway towards impact.