In this study, we introduce a novel continuous-flow cascade photocatalytic system specifically designed to efficiently remove sulfamethoxazole (SMX) from hospital wastewater, addressing the critical need for sustainable pharmaceutical wastewater treatment. The system utilizes a carbon sponge-based TiO2 photocatalyst synthesized via a hydrothermal process under mild conditions. The system’s design incorporates multiple stages in a cascade configuration, meticulously optimized to enhance photocatalytic efficacy, thereby significantly improving the rate of SMX elimination while minimizing energy consumption. The study encompasses comprehensive characterization of the photocatalyst, including matching its absorption spectrum to the emission spectrum of the light source, as well as fine-tuning key operational parameters such as catalyst quantity, flow rates, and cascade configuration. Real-world application tests confirm the system’s efficiency, achieving approximately 80 % SMX removal efficiency alongside a notable reduction in Chemical Oxygen Demand (COD) levels. Furthermore, the system’s energy efficiency, as reflected by an Electrical Energy per Order (EEO) value of 7.53 kWh/m3, highlights its potential for scalable and sustainable wastewater treatment solutions. This study not only contributes significantly to the field of environmental catalysis but also represents a significant advancement in sustainable environmental management, offering a promising solution to the urgent challenge of pharmaceutical pollution in water sources.