This article introduces the EU Horizon 2020 research project MIX-UP, “Mixed plastics biodegradation and upcycling using microbial communities”. The project focuses on the ambitious vision to change the traditional linear value chain of plastics to a sustainable, biodegradable based one. In MIX-UP, plastic mixtures containing five of the top six fossil-based recalcitrant plastics (PE, PUR, PP, PET, and PS), along with upcoming biobased and biodegradable plastics (bioplastics) such as PHA and PLA, will be used as feedstock for microbial transformations. The generated new workflow increases recycling quotas and adds value to present poorly recycled plastic waste streams. Consecutive controlled enzymatic and microbial degradation of mechanically pre-treated plastics waste combined with subsequent microbial conversion to polymers and value-added chemicals by mixed cultures. Through optimization of known plastic-degrading enzymes by integrated protein engineering, high specific binding capacities, stability, and catalytic efficacy towards a broad spectrum of plastic polymers under high salt content and temperature conditions will be achieved. Another focus lies in the search and isolation of novel enzymes active on recalcitrant polymers. MIX-UP will also enhance the production of enzymes and formulate enzyme cocktails tailored to specific waste streams. In vivo and in vitro application of these cocktails enables stable, self-sustaining microbiomes to convert the released plastic monomers selectively into value-added products, key building blocks, and biomass. Any of the remaining material recalcitrant to the enzymatic activity will be recirculated into the process by physicochemical treatment. The Chinese-European MIX-UP is a multidisciplinary and industry-participating consortium to address the market need for novel sustainable routes to valorize plastic waste streams. MIX-UP realizes a circular (bio) plastic economy and will contribute where mechanical and chemical plastic recycling show limits.