Co-existence of pollutants, specifically heavy metals and organic compounds, as well as multi-heavy metals, in wastewater presents a significant global environmental and public health concern. The combined presence of these pollutants can result in a synergistic increase in toxicity, making the simultaneous removal of heavy metals and organic contaminants a complex challenge. Cadmium sulfide-based photocatalyst-microbe biohybrids, which integrate the advantages of whole-cell biological catalysts and semiconducting nanomaterials, have garnered considerable interest. These biohybrids offer benefits such as the capacity for heavy metal ion recycling, enhanced remediation efficiency, and the simultaneous removal of combined pollutants. This review begins by outlining the strategy for developing CdS-based biohybrid systems. Subsequently, it explores the application and mechanisms of remediation facilitated by these systems. The current challenges and future perspectives for biohybrid systems are also discussed. Finally, the review highlights the potential of synthetic biology strategies for optimizing and constructing biohybrid systems.