There is a considerable debate in the literature regarding the real impact of tourism on the environment and human communities, specifically with respect to tourism’s openness to sustainable innovation. The way in which the different forms of tourism and entrepreneurial and managerial initiatives respond to the new economic, technological, social and environmental challenges acquire considerable importance for academics, practitioners, decision makers and consumers. The purpose of this research is to assess the potential for sustainable innovation in spa and health tourism in a relevant area in Romania through a survey-based study of both entrepreneurs who own a tourist accommodation unit, as well as top and middle managers from large tourism enterprises. The results of our research show that the development of spa and health tourism offers multiple examples of good practices, and that stimulating innovative entrepreneurial initiatives can lead to a sustainable reinvention of the tourism and local economy, in line with the international health tourism market. In the case of small businesses, even though sustainable initiatives are present, they are at an earlier stage and are less diversified compared to hotels, the scope of innovation is smaller and their motivation weaker. In other words, a large part of the objectives of modernization and sustainability in spa and health tourism (equipment, services, qualification and hiring of employees, sustainable and environmentally friendly orientation) are the responsibility of large hotel resorts. This research provides valuable insights into the ongoing debate surrounding the impact of tourism on the environment and local communities, with a specific focus on the potential for sustainable innovation in spa and health tourism within a significant region of Romania.