In aquatic environments, the coexistence and interaction of multiple the pollutants complicate remediation process. This study focuses on developing a defective-enriched S-scheme heterojunction of K3PW12O40@WS2 (KPW@WS2) with hollow structure for the simultaneous removal of tetracycline (TC) and hexavalent uranium (U(VI)) in wastewater. The internal electric field (IEF) within this heterojunction plays a crucial role in efficiently separating photo-generated carriers, creating high reduction and oxidation active sites. The band structure and optical properties suggest that WS2-Vs have a narrower band gap energy compared to conventional WS2, leading to improved charge carrier separation and transfer rates. Density functional theory (DFT) calculations support the reduced recombination of electron-hole pairs in WS2-Vs due to the presence of S vacancies. Experimental results reveal a synergistic effect between the removal of TC and U(VI), with a significant increase in the reaction rate constant for the reduction of U(VI) to 0.0426 min−1, 1.6 times higher than in a single U(VI) reduction system. Additionally, the reaction rate constant for the oxidation of TC also rises from 0.0573 to 0.0729 min−1. The study also delves into the photocatalytic mechanism, degradation pathways, and intermediate products. Overall, this research offers an innovative strategy for simultaneous pollutant removal and optimizing photocatalytic redox reactions to enhance solar energy utilization.