Treating disease according to precision health requires the individualization of therapeutic solutions as a cardinal step that is part of a process that typically depends on multiple factors. The starting point is the collection and assembly of data over time to assess the patient’s health status and monitor response to therapy. Radiomics is a very important component of this process. Its main goal is implementing a protocol to quantify the image informative contents by first mining and then extracting the most representative features. Further analysis aims to detect potential disease phenotypes through signs and marks of heterogeneity. As multimodal images hinge on various data sources, and these can be integrated with treatment plans and follow-up information, radiomics is naturally centered on dynamically monitoring disease progression and/or the health trajectory of patients. However, radiomics creates critical needs too. A concise list includes: (a) successful harmonization of intra/inter-modality radiomic measurements to facilitate the association with other data domains (genetic, clinical, lifestyle aspects, etc.); (b) ability of data science to revise model strategies and analytics tools to tackle multiple data types and structures (electronic medical records, personal histories, hospitalization data, genomic from various specimens, imaging, etc.) and to offer data-agnostic solutions for patient outcomes prediction; (c) and model validation with independent datasets to ensure generalization of results, clinical value of new risk stratifications, and support to clinical decisions for highly individualized patient management.