This study aims to evaluate energy reduction potential and effluent quality impacts of operational and structural optimization strategies in a full-scale municipal wastewater treatment plant in Vietnam using integrated process simulation tools. A combined modelling approach was applied using BioWin 6.1 and CapdetWorks 4.0 to simulate and compare multiple operational scenarios. The analysis focused on aeration scheduling, dissolved oxygen (DO) control, airflow regulation, and the replacement of an aerated selector with a mechanically mixed system in a sequencing batch reactor (SBR)-based configuration. Historical plant data were used for model initialization, and multiple optimization scenarios were developed to assess trade-offs between energy consumption and treatment performance under varying operational conditions. Simulation results showed that optimizing aeration duration and control parameters led to significant reductions in energy demand. The most efficient configuration achieved up to 67% reduction in energy consumption through shortened aeration cycles, while replacing aerated selectors with mechanical mixers yielded up to 50% reduction in specific operational components. The combined optimal scenario resulted in an overall energy saving of up to 83% (0.0161 kWh/m³). Across all simulated cases, effluent quality remained within national discharge standards, with only minor variations in COD, BOD, nitrogen, and phosphorus concentrations compared to the baseline configuration. The study is limited by its reliance on simulation-based results rather than full-scale experimental validation, and uncertainties associated with model calibration and default parameter assumptions. Despite these limitations, the findings provide practical insight into cost-effective energy optimization strategies that do not require major infrastructure reconstruction. Overall, the originality of this work lies in the integrated application of BioWin and CapdetWorks for combined energy–process optimization of an SBR-based municipal WWTP in a tropical developing country context. The study highlights the critical role of aeration management and selector configuration in reducing energy demand while maintaining effluent compliance.