Alpine Space (AS) Smart Specialisation Strategies (S3) were adopted to strengthen innovation and competitiveness by transforming economic structures through the identification of local excellence and by the development of new combinations of existing capacities. Recent experience gained in the Interreg-project S3-4AlpClusters shows that multi-national governance structures for focused cooperation in S3-implementation are critically missing. There is a persistent funding gap for AS cross-regional research, development and innovation (RDI) projects targeting S3 opportunities of particular relevance and including actors of new value chains (VC), from research to market. AS regions must inter-link their local assets and individual excellent capacities to address grand challenges in future European RDI. Dynamic areas with significant impact are related to megatrends in circular-bioeconomy and health-economy (CBH) that will tremendously impact the way of our status-quo economy. These fields are of high importance for strategic priorities under EUSALP. To tap into these synergies and unearth opportunities for innovation, cross-regional and cross-sectoral cooperation is imperative. ARDIA-Net overcomes this challenge by developing an Alpine RDI Area (ARDIA) for tailor-made S3 cooperation across regions by developing a funding framework and projects for addressing CBH megatrends across the AS. It draws on a partnership involved in policy deployment. ARDIA introduces an effective, framework for future cross-regional and interdisciplinary RDI projects enhancing VC inter-connection, investments, commercialisation, realise ESIF-H2020 synergies and ultimately upscaling AS efforts. It is thus a valuable contribution towards mission-oriented RDI in post 2020 policy frameworks. The project empowers governance for fostering S3 cooperation (eg synergies within S3: digitization, health, materials, food) for business support organisation, Academia and SME.