DeuS is a 9-country project promoted by regional VET providers and cultural and creative industries representatives, variously linked to research and technological centres and public players, that even stand for 4 European Capitals of Culture, among past, presents and future designated cities. It lays its groundwork in the Open Design School pilot initiative promoted under ECoC Matera 2019, thought to be an open laboratory pivotal to the successful implementation of the ECoC programme. The project organizes a steady network to challenge the concept of urban sustainable development underpinning the Open Design School. It is in-depth discussed, tested and improved by benefiting from know-how, expertise, best practices and lessons gathered within close and comparable experiences from partners and stakeholders. It strives to enable EU regional environments and research-driven settings – both physical (Creative Open Spaces) and virtual (a multi-sided Creative Knowledge Platform) – that allow VET systems, professionals, researchers, policy-makers and local people to engage in iterative processes of innovation and problem solving to generate solutions to local challenges (RIS3) and deliver them to SMEs and other entrepreneurs, public bodies and everyone who need them. This approach enables educational opportunities in design and innovation, critical thinking and entrepreneurship to find creative and cost-effective ways to connect within and across regional territories. Cooperation and education provide opportunities to access skills, competences and research infrastructures. Players are all involved in feedback-loops allowing creative innovators to be more responsive and attractive. They can iterate, learn, and share with others, feeding innovation. Furthermore, joiners are allowed to assess social needs at local level and iteratively evaluate and improve their solutions by a trail-and-error approach that encourage sharing of lessons learned and best practices.