Adopting Industry 4.0 technology is anticipated to enhance industry efficiency, productivity, and product customization. Nevertheless, this transition may induce significant alterations to corporate systems, presenting numerous challenges that industries must navigate during implementation, especially for small-to-medium industries. Hence, this study examines the interrelationships among barriers and identify the critical obstacles to implementing Industry 4.0 in small-to-medium industries within the food and beverage sector in Indonesia. To achieve this, an integrated methodology combining the Delphi Method, Interpretive Structural Modeling (ISM), and Matrix Impact with Cross Multiplication Applied to Classification (MICMAC) analysis is employed. The barriers to Industry 4.0 implementation are conceptualized using the Technology-Organization-Environment (TOE) framework. This study found that the MICMAC analysis supports the model derived from the ISM results. Insufficient government support, the need for investment, insufficient Industry 4.0 training, and insufficient standardization efforts are critical barriers that are located in the independent cluster according to the MICMAC analysis and are positioned at high levels in the ISM model.