REPO4EU is an EU-funded initiative focused on drug repurposing, uniting 28 partners from 10 countries to create a comprehensive platform for mechanism-based drug repurposing. This initiative aims to advance precision medicine and reduce costs and development time. The platform emphasizes bioinformatics, 1precision diagnostics, 2and innovative clinical trials to redefine disease treatment and improve patient outcomes. Drug repurposing offers advantages such as low costs and rapid patient benefits but faces high failure rates due to limited resources among small companies and academic groups. To mitigate this risk, REPO4EU combines drug repurposing with a novel disease approach, constructing protein-protein interaction or signaling modules 3derived from disease-associated genes. Therapeutically, network pharmacology 4targets multiple proteins within a module to preempt feedback mechanisms that may reduce single-drug efficacy. Diagnostics are crucial for applying this therapeutic approach to patients sharing the same causal mechanism. These theranostic pairs are validated in phase IIa proof-of-concept trials. Over its seven-year duration, REPO4EU aims to establish a permanent European infrastructure named REPOSystem, synergistic with existing health-related infrastructures like BBMRI-ERIC, eu-openscreen, and INFRAFRONTIER, all sharing the goal of precision medicine. This approach has been validated in two cardiovascular and one cancer indication.