The SYMBIO project provides European regional communities with tools and methodological approaches to building bio-based business models based on circularity by-design and industrial symbiosis. Thanks to tools for integrating big data and artificial intelligence, SYMBIO shapes 10 symbiotic business models with high-profitability sustainability replicable at the EU level to increase bio-based products on the market and provides a system to modelling, measure and monitor symbiosis and its social, economic and environmental impacts. SYMBIO methodology will be designed, tested and validated in 12 EU pilot regions (Lombardy, Piedmont, Veneto, Friuli-Venezia Giulia, Emilia-Romagna, Carinthia, Slovenia, Croatia, Andalusia, Bruxelles Capital, Wallonia, Flanders) that have been selected based on the estimation of their bio-based resources defined by raw material availability, socio-economic indicators, intangible networks and infrastructures and potential for development of CBE close-to-market supply chains and current trends. Involving all supply chain actors in a quadruplex approach will help unlock and stimulate local development potential by promoting sustainable, innovative, tangible and participatory pathways to the green transition through an inclusive bottom-up CBE nexus.