NAVIGATOR is an Italian regional project boosting precision medicine in oncology with the aim of making it more predictive, preventive, and personalised by advancing translational research based on quantitative imaging and integrative omics analyses. The project’s goal is to develop an open imaging biobank for the collection and preservation of a large amount of standardised imaging multimodal datasets, including computed tomography, magnetic resonance imaging, and positron emission tomography data, together with the corresponding patient-related and omics-related relevant information extracted from regional healthcare services using an adapted privacy-preserving model. The project is based on an open-source imaging biobank and an open-science oriented virtual research environment (VRE). Available integrative omics and multi-imaging data of three use cases (prostate cancer, rectal cancer, and gastric cancer) will be collected. All data confined in NAVIGATOR (i.e., standard and novel imaging biomarkers, non-imaging data, health agency data) will be used to create a digital patient model, to support the reliable prediction of the disease phenotype and risk stratification. The VRE that relies on a well-established infrastructure, called D4Science.org, will further provide a multiset infrastructure for processing the integrative omics data, extracting specific radiomic signatures, and for identification and testing of novel imaging biomarkers through big data analytics and artificial intelligence.