The relentless scourge of tuberculosis, malaria and emerging infectious diseases continues to threaten lives in Africa. The problem lies in the inadequate understanding of disease dynamics, limited capacity in genomics and fragmented data sharing. In this context, the EU-funded PANGenS project aims to transform Africa’s approach to disease control by leveraging genomic epidemiology. Its overall mission is to equip the continent with cutting-edge skills in genomics, data management and biobanking while promoting robust data sharing. With an arsenal of hypotheses, including improved surveillance, better responses to emerging pathogens and enhanced diagnostics, PANGenS aims to enhance disease surveillance, empower the next generation of African scientists and foster robust research collaborations within the continent. To establish infrastructure and expertise, we will conduct prove-of-concept projects applying genomic epidemiology to the two priority diseases in Africa: TB and Malaria. Institutions from the following countries are taking part in the study: Ghana, Mozambique, Tanzania, Namibia, Nigeria, Gabon, Benin, Togo, Liberia, South Africa, The Gambia, Switzerland, The Netherlands and Germany. The Noguchi Memorial Institute of Medical Research in Ghana and the German Research Center Borstel, Leibniz Lung Center are the coordinating institutes.