PROTECT-CHILD is a project that aims to improve the outcomes of rare pediatric transplant patients by integrating multiple sources of high-throughput data from registries, hospital-based and public repositories, complying with ongoing initiatives such as the European Open Science Cloud (EOSC) and the European Health Data Space (EHDS). The project focuses on the co-design of a secure and privacy-preserving infrastructure, harmonization of data standards, and creation of a public/private infrastructure for assembling large datasets to improve clinical outcomes. The project involves top-level expertise from a consortium of technology specialists, data standardization experts, and High-Performance Computing (HPC) centers, as well as clinical experts, legal experts, patients’ representatives, and policy makers. The project is aligned with EHDS and General Data Protection Regulation (GDPR) principles and aims to empower secure and compliant processing, analysis, and sharing of sensitive personal data, including genomics, while preserving data privacy and security.