In the context of Industry 4.0, Supply Chain Management (SCM) faces challenges in adopting advanced optimization techniques due to the “black-box” nature of most AI-based solutions, which causes reluctance among company stakeholders. To overcome this issue, in this work, we employ an Interpretable Artificial Intelligence (IAI) approach that combines evolutionary computation with Reinforcement Learning (RL) to generate interpretable decision-making policies in the form of decision trees. This IAI solution is embedded within a simulation-based optimization framework specifically designed to handle the inherent uncertainties and stochastic behaviors of modern supply chains. To our knowledge, this marks the first attempt to combine IAI with simulation-based optimization for decision-making in SCM. The methodology is tested on two supply chain optimization problems, one fictional and one from the real world, and its performance is compared against widely used optimization and RL algorithms. The results reveal that the interpretable approach delivers competitive, and sometimes better, performance, challenging the prevailing notion that there must be a trade-off between interpretability and optimization efficiency. Additionally, the developed framework demonstrates strong potential for industrial applications, offering seamless integration with various Python-based algorithms.