The tourism sector has witnessed continuous development over the last few decades, overcoming various challenges and crises. This resilience underscores the remarkable diversity of managerial and entrepreneurial initiatives capable of meeting the ever-growing and unpredictable global demand. Our objective is to explore the perceptions of factors and opportunities that encourage the launch and management of businesses in health and spa tourism utilizing a qualitative methodology. Our conclusions are based on the analysis of 32 hotel managers’ and small business owners’ interviews in a relevant tourist resort in Romania. This study reveals that all four types of identified opportunities and drivers influencing business creation and management in health and spa tourism (i.e., improving work quality and independence, professional and personal development, responses to opportunities, and upgrading existing services) are substantially influenced by gender, relevant work experience, and education. The novelty of our research lies in highlighting the influence of these drivers according to a specific context given by the size, management type, and ownership structure of tourism ventures, as well as the difference between large hotel managers and small business owners in terms of their perception and goals. We acknowledge that the limited number of interviewees and the spatially bound context of the research may have an effect on the relevance of the results. This study’s findings underscore the necessity for compromise and collaboration among diverse stakeholders in the tourism industry, particularly when developing long-term strategies for health and wellness destinations. This collaborative approach plays a critical role in promoting the well-being and prosperity of individuals, businesses, and the entire local community.