In the context of globalization, regions see themselves more and more exposed to a competition about qualified work force, company settlements, employment and European funds. In parallel, global challenges like an aging population or climate change ask for regional solutions and collaborations have become vital. Cross-border regions across Europe have developed to reduce barrier effects and foster new development potentials. The aim of the following study is to analyse the effects of the implementation of cross-border regions on the competitiveness of local companies and institutions. Therefore, a comparative case study of the European Region Donau-Moldau and the Euregio Meuse-Rhine has been designed. The analysis shows that the potential of CBRs relies in the fact to join forces and competencies and that these collaborations address relevant topics to foster the competitiveness.