The aim of INTERVENE is to develop and test next generation tools for disease prevention, diagnosis, and personalised treatment utilizing the first US-European pool of genomic and health data and integrating longitudinal and disease-relevant -omics data into genetic risk scores. Resulting in unprecedented potential for prediction, diagnosis, and personalised treatments for complex and rare diseases. Some of the largest biobanks in Europe and one in the USA will be securely linked and harmonized in a GDPR-compliant repository with data from more than 1.7 million genomes. INTERVENE will demonstrate the potential and benefits of powerful AI technologies on the next generation of integrative genetic scores (IGS). The clinical and economic benefits of IGS will be evaluated in key disease areas with major public health burden. Here, the newly developed IGS will be taken into clinical environment and their real-world benefits will be evaluated together with clinical experts, European patients advocate groups and medical societies and considering regulatory and ethical implications. Thus, a framework for legally and ethically responsible translation into wider clinical practice will be developed. Moreover, the partners will develop and test the role of IGS in several rare diseases as well as COVID-19 infection and severity. Importantly, to support the application of IGS via public-private partnerships including clinical practitioners, an AI-enabled federated data analysis platform, the ‘IGS4EU’ platform, will be developed for automated IGS generation and interpretation for end-users. Additionally, the IGS4EU platform will allow access of the INTERVENE data and the methodology know-how to the AI community through a competition-based benchmarking environment. In the long term, the IGS4EU platform aims to grow the disease coverage and enable a wide adoption of IGS as a gold standard in clinical research and practice.