Counteracting high attrition rates in oncology drug development and providing optimal therapeutic management of cancer patients require preclinical models that properly recapitulate the complexity and diversity of human tumours. Patient-derived tumour xenografts (PDXs), established by transplanting tumour fragments into immunodeficient mice, are being widely embraced by the scientific community as preclinical tools for target and biomarker discovery. The overall goal of EDIReX is to establish a cutting-edge European infrastructure offering Trans-national Access (TA) of PDX resources to academic and industrial cancer researchers, including the distribution of cryopreserved samples to third parties, the structured biobanking of user-developed models, and the performance of efficacy studies. To ensure interoperability in services, TA initiatives will be backed by Networking Activities (NAs); these will be mainly centred around the establishment of standard procedures for PDX quality control, long-term storage and therapeutic mouse trials. NAs will also entail the adoption of shared ethics parameters for animal experimentation, the wide dissemination of services and project results, and the design of plans to ensure sustainability of the infrastructure. User outreach will be maximised by Joint Research Activities through a three-pronged approach: i) the implementation of a public Data Portal for efficient and user-friendly query and visualisation of clinical, molecular and pharmacological annotation of the models; ii) a cross-validation mouse trial to harmonise inter-laboratory procedures, thus improving the quality and reliability of service provision; and iii) the development of exploratory, more advanced PDX-based preclinical platforms, such as orthotopic and humanised models and in vitro PDX-derived cells. Capitalising on all these assets, EDIReX will contribute to structuring the European Research Area and global cooperation of research infrastructures.