We are currently experiencing rapid transformation in technologies and society. Due to the convergence of various megatrends, these changes have considerable impacts on everyday life. Our study aims to identify relevant strategies for the digital future of a macro-region (Tyrol, South Tyrol and Veneto). The study conducts semi-structured interviews with representatives of companies, universities and local governments, using the approach of a triple helix model. Based on the empirical analysis, we develop an action plan for the digital transformation of the macro-region.