Evidence-based Health Tourism (EHT) is a branch of general tourism foreseeing tourists to travel with the aim of receiving healing treatments or enhancing a specific mental, physical or spiritual health condition through medically-proven offers. EHT competitiveness is increasingly linked to the sustainability and exploitation of unique natural resources of tourism destinations, which often lack the access to knowledge and networks of stakeholders to improve their offerings, even by the use of digital tools. This study illustrates a Collaborative Design approach for the development of an ontology-based Decision Support System for modelling the relationships between the available natural resources, the value offerings and the target groups of EHT destinations in the Alpine region. The Collaborative Design approach foresees the involvement of end-users (i.e. EHT destinations, stakeholders and tourists) as both sources of knowledge and validators of the ontology and its outputs, aiming to inform decision-making processes in a shared knowledge model.