Religious travels play a significant role in tourism, and the optimal connection between spirituality and commercialization of the brand of religious tourism destinations should be guided by a comprehensive analysis of the stakeholders’ interests. The purpose of the study is to investigate the relationship between spirituality and commercialization of religious tourism brand in Mashhad, using the qualitative approach and grounded theory. Data collection was based on theoretical foundations, the study of upstream documents, and conducted deep, open, semi-structured interviews with experts that were selected purposefully. To analyze the data, a continuous comparison method has been used during three stages of open, axial, and selective coding. The results showed that 153 concepts in the interaction of spirituality and the brand commercialization exist in 5 contextual categories, 5 casual categories, 3 intervention categories, 3 strategic categories, 10 consequence categories and 3 categories of (inconsistency of national macro-measures with the interests of urban stakeholders, intra-organizational and inter-organizational conflict and partial optimization) as barriers to the implementation of strategies.