SYSTEMEU is an initiative aimed at transforming European innovation ecosystems through open innovation by fostering digitalization in healthcare, energy, and mobility. It unites five regional ecosystems, fostering inclusivity and collaboration among universities, incubators, public organizations, government agencies, and innovation centers from Germany, Romania, Portugal, Bosnia and Herzegovina, and Spain. SYSTEMEU addresses the issue of traditional innovation efforts' limited focus on societal and environmental transformation, introducing a systemic and long-term perspective. By fostering a collaborative and interdisciplinary environment, SYSTEMEU will enable adaptable policies and stimulate economic vibrancy, enhancing societal well-being and advancing European innovation. SYSTEMEU promises to create interconnected, inclusive, and more efficient innovation ecosystems, strengthen cross-border network collaboration through six cross-regional projects in project duration and others after the project end, expand global cooperation through existing networks of European actors and ecosystems, promote gender equality, and reduce territorial inequalities in access to innovation support, aligning with EU policies and strategies. SYSTEMEU's innovative approach aims to usher Europe into a regenerative world.