In the era of Industry 4.0, manufacturing organizations are compelled to adopt technologies and manufacturing systems that can meet the needs like better quality products, flexibility in manufacturing, and better productivity. Because Reconfigurable Manufacturing System (RMS) can meet the majority of the needs of a dynamic market, it is necessary to identify the risk factors of its implementation so that practitioners can take care of them to improve the adoption and success of the manufacturing system. The purpose of this paper is to identify the risk factors of RMS implementation through an extensive literature review and model them using a hybrid ISM-MICMAC analysis method. The ISM method is used to obtain the structural framework of RMS risk factors while taking into account the challenges of the Industry 4.0 era, whereas the MICMAC analysis is used to obtain the driving and dependence power of risk factors so that risk factor interdependencies can be analyzed. The findings show that the risk of unsupportive management, employee resistance risk and risk of financial loss has the maximum driving power, whereas the risk of delays and risk of inadequate product quality/flexibility has the maximum dependence power. The authors believe that this will assist RMS and Industry 4.0 practitioners in identifying implementation risks at specific stages of implementation to avoid implementation delays. This could be a first attempt to identify RMS risk factors in the context of Industry 4.0, including their modeling using a hybrid ISM-MICMAC approach.