The Beyond 1 Million Genomes (B1MG) consortium will establish the support and coordination structure for the European 1+ Million Genomes initiative (1+MG), which is based upon the commitment of 20 European Member States and Norway that have signed the Declaration ‘Towards access to at least 1 million sequenced genomes in the EU by 2022’. Collectively, these countries have committed to establish a cross-border federated network of national genome collections associated with phenotypic data, consented for advancing health and medicine practices across Europe. Europe is uniquely placed to take on this challenge and position itself as a global leader in this field. B1MG will go ‘beyond’ the 1M genome target and ‘beyond’ the 20 signatory countries. The project will collaborate with an array of international initiatives and consult a range of stakeholders to support the creation of a pan-European genome-based health data infrastructure, encompassing data quality and exchange standards, access protocols and legal guidance. Recommendations will be translated to a B1MG maturity level model that provides concrete guidance on the steps required to implement personalised medicine, a healthcare approach that takes into account a person’s genetic make-up, at local, regional and national-scale. Personalised medicine is expected to bring significant socio-economic benefits, including more efficient national health systems. Faster and more accurate diagnosis, the development of pharmacogenomics and advancement of preventative medicine will lead to better health, quality of life of patients and increased life expectancy. This will be captured in a methodology for economic evaluation, forming the basis of future business-cases for implementation in the health sector.