The 21st century witnesses increased incidence of epidemics (Zika, dengue, Ebola, SARS), with as latest highlight the recent COVID-19. Following the outbreak of several infectious diseases during the last few decade, the need for generating real-time pathogen genomic data for public health action has become more important than ever. In the African context, infrastructure, human resource capability, data analysis, including bioinformatics, lack of linkage between clinical, epidemiological, and pathogen genomic data as well the interaction between clinicians, researchers and decision makers are some of the major challenges. The aim of the EpiGen project is to build a capacity for integrated pathogen genomic surveillance for informed public health decision process. The overarching specific objectives include strengthening collection and analysis of clinical and epidemiological data, enhancing the capacity and capability for pathogen genomic sequencing, including strengthening the laboratory infrastructure, human work force, pathogen genomic data analysis, and the integration of metadata with genomic data, developing and implementing innovative digital diagnostic platforms, creating semi-real time mobile phone applications for policy decisions, and promoting communities of practice and knowledge exchange through fostering African collaboration and networking in the domain of pathogen genomic surveillance for infectious diseases. EpiGen project’s multi-disciplinary consortium is drawn from several institutions from Ethiopia engaged in National Public Health Programs, and EU partners (The Netherlands, Spain and Germany). Overall, the model approach proposed by EpiGen will enhance Ethiopia’s national effort in mitigating the threat of infectious diseases. The implementation of a national genomic-informed surveillance for infectious diseases will play significant public health role towards contributing to disease prevention and control programmes in Ethiopia and beyond.