One of the most pressing and complicated issues European regions face nowadays is how to introduce, develop and maintain Research and Innovation (R&I) regional policies that promote sustainable development, societal inclusion and citizen participation under a framework of democratic governance. This is the so-called “Regional Dilemma”. The aim of RRI2SCALE is to tackle the Dilemma of four pilot European participating territories by empowering the regional ecosystems and boosting their future development trajectories in the R&I domain. The pioneer regions that have been selected to participate are: Hordaland (Norway), Overijssel (Netherlands), Kriti (Greece) and Galicia (Spain). In other words, the project seeks to embed Responsible Research and Innovation (RRI) processes into the current R&I ecosystems. This can be achieved through sustainable and inclusive institutional evolution in the governance structures of the pilot regions. In order to meet its targets, RRI2SCALE attempts to map and understand the regions engaged, how some RRI elements are currently incorporated in their ecosystems, the societal perceptions towards these elements, and how much space for improvement is available. The project’s pilot actions are operationalised within the triple scheme of “smart cities – transport – energy”, which are considered institutional vehicles for sustainable growth. The ultimate end is to introduce a new democratic model of governance in the regional R&I ecosystems.