Europe is confronted with a multitude of health challenges for which strong research and innovation efforts may bring solutions. The strategies and policies governing R&I, however, need to be harmonized across different levels (EU, national, regional) and transcend geographical boundaries to defragment European research efforts. The need for European cross-border alignment of R&I efforts became particularly obvious during the COVID pandemic. Although there is an immense potential throughout Europe to become the preferred global hub to conduct clinical studies and trials, Europe largely failed to secure this potential. Besides the imminent urgency to provide a response in case of a pandemic, aligning R&I strategies and policies isalso crucial to develop healthcare of the future, which will be personalised and preventive, building on the convergence of cutting-edge technologies, such as bio-, nano-, digital technologies and engineering and integration of several types of data, including genomic data, health data, and real-world data. The transformative potential of such convergence, however, is frequently hindered by the challenge of translating scientific knowledge into practical innovations and effectively incorporating these innovations into healthcare systems as well as the lack of standardisation and harmonisation. The European partnerships and access to high-end research infrastructures play a pivotal role in addressing the fragmentation of European R&I efforts and realising the ultimate goals and ambitions of establishing Europe as a lead region in the world providing R&I-based answers to complex health challenges.