Head and Neck Cancer (HNC) is a deadly disease affecting more than 630.000 patients each year in the EU. Treatments may be extremely impairing with hard impacts on aesthetics, swallowing, breathing and patients’ quality of life. HNC presents extremely different biological characteristics, which would significantly benefit from personalized patients’ classification and personalized treatment. Despite significant advances in therapies, at present treatment decisions are taken on a “one size fits all” approach, based on few clinical and risk factors, the so-called TNM system, as no biomolecular predictors of disease outcome are yet validated. Using AI and advanced modelling techniques, SuPerTreat will analyze the different biomolecular characteristics of HNC that discriminate patients into high/medium/low-risk subgroups in the aim to identify how combined clinical, lifestyle and biomolecular factors concur to response to treatments, recurrence and survival. The so generated knowledge will inform personalized treatment.