The fourth industrial revolution, fueled by automation and digital technology advancements, enables us to manage manufacturing systems effectively. Its deployment in enterprises has now become increasingly important in developed and emerging economies. Many experts believe that barriers associated with Industry 4.0 implementation are critical to its success. Therefore, this study aimed to identify the major hurdles to Industry 4.0 adoption and reveal their interrelationships. Initially, the literature was thoroughly studied to determine the sixteen barriers impeding I4.0 adoption. Then, based on experts’ opinions, an integrated fuzzy-DEMATEL approach was utilized to examine the most significant challenges to I4.0 deployment. The results demonstrated the distribution of barriers in which the economic dimension played a decisive role, affecting technological, regulatory, and organizational dimensions. As observed in the barrier mapping, the lack of qualified workforce was a typical adoption barrier. Finally, the mitigation strategies developed would help managers to overcome the identified critical obstacles.