The palm oil industry generates a considerable amount of waste, known as palm oil mill effluent (POME), which is characterized by high levels of chemical and biological oxygen demand (COD and BOD). The anaerobic digestion of POME is a potential solution for generating biogas, a renewable energy source that can be used for power generation. However, optimizing biogas production from POME is a challenging task, particularly at the industry scale due to the complex nature of the waste stream. This study aimed to improve the performance of an existing POME-based biogas plant through simulation and optimization. The POME treatment process was simulated using SuperPro Designer software. The simulated results were validated against data obtained from the existing plant, including the environmental properties of COD, BOD, total suspended solids (TSS), and total solids (TS), as well as the composition of the biogas produced. The simulation results showed good agreement with the existing plant data, although some parameters had a high relative difference due to assumptions made during the simulation. The process parameters, including the recirculation ratio and hydraulic retention time, were optimized using Design Expert software. The optimized parameters obtained were a recirculation ratio of 148 and an HRT of 22 days, resulting in a maximum biogas flow of 859 m3/h, corresponding to a methane yield of 0.259 m3 CH4/kgCOD removed. Confirmatory experiments were conducted over a period of 3 months using the optimized variables in the biogas plant. The results showed a high level of consistency between the predicted and experimental values with a percentage error difference ranging from 0.03 to 2.3 . This study's novelty lies in the integration of simulation and optimization tools to improve the performance of POME-based biogas plant. The findings of this study have significant implications for sustainable development in the palm oil industry, providing an efficient and cost-effective approach for treating POME and producing renewable energy. © 2023