Spa towns represented, for decades, a point of reference for the European panorama of health, tourism and cultural exchange. They have been the first tourist destination in the modern sense, as well as a manifesto for a renewed demand of quality and laboratories for architectural and urban experimentations. A product of territorial relations, they have been able to aggregate ideas, capital and skills in a generative logic. However, from the second half of the 20th Century, these cities underwent a series of structural changes related to health and tourism trends that deeply affected all levels of their local systems. Today, these places are witnessing numerous episodes of degradation and abandonment of their built cultural heritage. Promoting a place-based approach, this paper argues that spa towns could be reconsidered as strategic resources in the construction of the territorial capital and that adaptive reuse practices, if integrated into strategic visions, can represent a driver for the activation of a sustainability transition based on ‘fully circular’ processes. Here, the abandoned built cultural heritage represents an opportunity space, a potential catalyst of innovative synergies, and a meeting point between local and territorial interests. While referring both to theoretical profiles and applied research experiences, the paper frames urban transformation and adaptive reuse processes as an integrated challenge within change management logics. Finally, the paper proposes a set of thematic recommendations in order to stimulate the creation of receptive environments for change and deal with the different times, scales, actors and the economic and non-economic interests involved.