<p>Cancer remains a leading cause of global mortality, where early detection and continuous monitoring are critical for improving therapeutic outcomes. However, conventional diagnostic techniques suffer from high cost, long assay times, invasiveness, and limited sensitivity at early disease stages. In this context, electrochemical biosensors have emerged as promising alternatives due to their rapid response, cost effectiveness, low sample volume requirements, high sensitivity, and compatibility with point-of-care testing. Recent advances highlight the pivotal role of electrode materials in translating biomolecular recognition into reliable electrical signals, particularly for detecting cancer-associated biomarkers near clinically relevant threshold levels. Among emerging semiconducting materials, molybdenum disulfide (MoS₂) has attracted significant attention owing to its layered two-dimensional structure, tunable bandgap, abundant electroactive edge sites, and versatile surface chemistry. This review critically examines recent progress in MoS₂ nanohybrid based electrochemical biosensors for cancer detection, focusing on material design strategies, fabrication approaches, and biomarker-specific sensing architectures. Emphasis is placed on MoS₂ hybrid systems incorporating carbon nanostructures, metal nanomaterials, metal oxides, polymers, MOFs, and other nanostructures, as well as their roles in enhancing signal transduction and real-time applicability in clinical samples. Finally, current challenges are outlined towards developing clinically translatable electrochemical sensing systems for early cancer detection and disease diagnosis. Furthermore, this review highlights the potential of integrating semiconductor-based electrochemical sensors with threshold-based diagnostic strategies as a promising future direction for point-of-care cancer detection.</p> Graphical abstract <p></p>