In modern and cost-effective Wastewater Treatment Plants (WWTPs), processes such as aeration, chemical feeds and sludge pumping are usually controlled by an operating system integrated with online sensors. The proper verification of these data-driven measurements and the control of different unit operations at the same time has a strong influence on better understanding and accurately optimizing the biochemical processes at WWTP—especially energy-intensive biological parts (e.g., the nitrification zone/aeration system and denitrification zone/internal recirculation). In this study, by integrating a new powerful PreviSys with data driven from the Supervisory Control and Data Acquisition (SCADA) software and advanced algorithms such as Model Predictive Control (MPC) by using the WEST computer platform, it was possible to conduct different operation strategies for optimizing and improving the energy balance at a full-scale “Klimzowiec” WWTP located in Chorzow (Southern Poland). Moreover, the novel concept of double-checking online data-driven measurements (from installed DO, NO3, NH4 sensors, etc.) by mathematical modelling and computer simulation predictions was applied in order to check the data uncertainty and develop a support operator system (SOS)—an additional tool for the widely-used in-operation and control of modern and cost-effective WWTPs. The results showed that by using sophisticated PreviSys technology, a better understanding and accurate optimization of biochemical processes, as well as more sustainable WWTP operation, can be achieved.