The continuing demand for plastic products, the lack of appropriate recycling and the ubiquitous pollution of the environment with plastic waste pose a global challenge. An ambitious vision and considerable efforts are required to change the traditional value chain of plastics to a sustainable one, based on biodegradable plastics. In MIX-UP, plastic mixtures with five of the top six fossil-based recalcitrant plastics (PP, PE, PUR, PET, and PS), along with upcoming biodegradable plastics such as PLA and PHA, will be used as feedstock for microbial transformations, thereby generating a workflow that increases the recycling quota and adds value to poorly recycled plastics waste streams. Successive controlled enzymatic and microbial degradation of mechanically pre-treated plastics waste will be combined with subsequent microbial conversion to value-added chemicals and polymers by mixed cultures. We will optimize known plastics-degrading enzymes for high specific binding capacities, stability, and catalytic efficacy towards a broad spectrum of plastics polymers under high salt and temperature conditions by integrated protein engineering, and also isolate novel enzymes with activities on recalcitrant polymers. MIX-UP will also optimize the production of enzymes and formulate enzyme cocktails tailored to specific waste streams. Implementation of these enzymes, both in vitro and in vivo, enables stable self-sustaining microbiomes to convert the released plastic monomers selectively into at least six value-added products, key building blocks, and biomass. Any remaining material recalcitrant to enzymatic activity will be recirculated into the process after a physico-chemical treatment. The Chinese-European MIX-UP is a multidisciplinary and industry-driven consortium that addresses the market need for novel sustainable routes to valorise plastics waste streams. MIX-UP realises a circular (bio)-economy and could be a viable alternative for mechanical and chemical recycling.