Purpose- In many development programs in the third world, the expansion of small home businesses in rural areas has been mentioned as an efficient solution to advance the rural development process and improve the living conditions and income of rural residents. Therefore, the aim of this study is to prioritize the challenges of home business in rural areas of Sari County. Design/methodology/approach - The present study is an applied and descriptive-analytical, for which the method of documentary and survey (questionnaire) were used. The statistical population of the research consists of experts of the General Directorate of Cultural Heritage, Handicrafts and Tourism of Mazandaran Province and the Industry, Mine and Trade organization and the Agricultural Jihad organization in Sari County. Fifteen people were selected as a statistical sample. Six factors of economic and financial, infrastructure, education and innovation, insurance and law, marketing and skills were considered as home business challenges in rural areas of Sari County. In order to analyze the data, the combined DEMATEL method and interpretive structural modeling were used. Findings- The results showed that education and innovation, insurance and law and skills barriers are at the highest level of the model, and economic and financial, marketing, and infrastructure barriers are at the lowest level of the model. According to MICMAC analysis, economic and financial, and marketing barriers with strong impact and weak dependence were identified as the most important challenges for home businesses in rural areas of Sari County. Research limitations/implications - The absence of a comprehensive database for home businesses, especially in rural areas, poor cooperation of experts in completing the questionnaires is the limitation of this study. Creating and organizing a database of home-based businesses are suggested, especially in rural areas that have been less studied and arranging the study platform for other research in this field. Practical implications - Supporting home-based businesses based on local and indigenous capacities and knowledge is a solution that not only promotes the production and creates jobs for the villagers, but also has positive social consequences. Originality/value- The results of this research can be a guiding tool in the executive organizations in charge of issuing home business licenses (Agricultural Jihad Organization, Industry, Mining, and Trade Organization and Cultural Heritage, Handicrafts and Tourism Organization) and institutions supporting the vulnerable and poor groups (Imam Khomeini Relief Foundation and the Welfare Organization). It could also help the managers implement the prosperity of home businesses as effectively as possible.