Smart cities and smart regions are nowadays positioned at the intersection of digital technology, disruptive innovation and urban/rural environments for citizens, entrepreneurs and policy-makers and becoming ‘smarter’ by means of accelerating the adoption of digital technologies and by rapidly introducing solutions across all sectors of community activities. 5G, and the upcoming 6G, Big Data, IoT, AI and Cloud Computing are becoming an integral part of a city’s digital infrastructure, interwoven with people’s daily lives, changing our society in a historically unprecedented way. Many municipalities and regional authorities have already started taking into consideration these advances in their planning and daily operations. The HORIZON METACITIES Excellence Hub is a sustainable network that offers a common platform for collaboration, cross-fertilization and best practice sharing across borders, sectors and disciplines on knowledge production, circulation and use. Founded upon a joint R&I strategy, a nexus of collaborative links across sectors, joint research, innovation and outreach activities as well as business modelling and sustainability plans, the collaboration aims to benefit citizens, stakeholders and regional ecosystems.