The global development of wellness tourism has brought niche entrepreneurial opportunities for tourism planners to develop and diversify the destination market. Meanwhile, Iran enjoys enormous natural and cultural potentials which can attract wellness travelers through proper management and planning. Hence, this article has employed the grounded theory methodology (the emerging approach) to propose a guiding framework for identifying and commercializing entrepreneurial opportunities of wellness tourism in Iran. This aim is pursued through analysis of literature and discussion with related academic and industrial experts. To this end, a qualitative data collection method is adopted, and since the potential participants were limited and hard to find, a combination of targeted and snowball sampling is chosen to conduct extensive in-depth interviews to identify the most important factors engaged in wellness tourism entrepreneurship. Analyzing the gathered data through the manual coding process, the findings of this study show that the factors and components that influence and are engaged in the development of wellness tourism businesses can be covered in four categories; “ Macro Business Environment” , “ The Wellness Tourism Industry’ s Micro-environment” , “ Barriers and Challenges of Development” , and “ Effects and Consequences-Wellness Tourism Development” . The developmental strategies are categorized under the “ Identification and Commercialization Process” (as the core category of the research model), and cover the stages from market identification to the commercialization of wellness products and services, each containing several steps towards sustainable exploitation of wellness business opportunities and especially, wellness tourism entrepreneurship.