Advancements in wastewater treatment systems are imperative for mitigating environmental pollution and ensuring the sustainability of water resources. This chapter explores the integration of simulation and optimization techniques to enhance the performance of wastewater treatment systems. By combining advanced simulation models with optimization algorithms, operators can achieve improved efficiency, reduced costs, and enhanced environmental outcomes. This integrated approach enables real-time monitoring, predictive analytics, and optimal decision-making in the management of wastewater treatment processes. Case studies and examples illustrate the practical application and benefits of this approach in various contexts. Overall, this chapter highlights the significance of merging simulation and optimization methodologies to address the evolving challenges of wastewater treatment, paving the way for more sustainable and effective solutions.