This paper presents an integrated approach based on physical–mathematical models and numerical simulations to optimize sludge treatment using ultrasound. The main objective is to improve the efficiency of the purification system by reducing the weight and moisture of the purification sludge, therefore ensuring regulatory compliance and environmental sustainability. A coupled temperature–humidity model, formulated by partial differential equations, describes materials’ thermal and water evolution during treatment. The numerical resolution, implemented by the finite element method (FEM), allows the simulation of the system behavior and the optimization of the operating parameters. Experimental results confirm that ultrasonic treatment reduces the moisture content of sludge by up to 20% and improves its stability, making it suitable for agricultural applications or further treatment. Functional controls of sonication and the reduction of water content in the sludge correlate with the obtained results. Ultrasound treatment has been shown to decrease the specific weight of the sludge sample both in pretreatment and treatment, therefore improving stabilization. In various experimental conditions, the weight of the sludge is reduced by a maximum of about 50%. Processed sludge transforms waste into a resource for the agricultural sector. Treatment processes have been optimized with low-energy operating principles. Additionally, besides utilizing energy-harvesting technology, plant operating processes have been optimized, accounting for approximately 55% of the consumption due to the aeration of active sludge. In addition, an extended analysis of ultrasonic wave propagation is proposed.