Biosensors have emerged as a promising tool for cancer diagnosis and monitoring due to their ability to rapidly and sensitively detect cancer biomarkers. Biosensors can be classified based on the type of biorecognition element and transducer used, with common techniques including electrochemical, optical, and piezoelectric biosensors that can detect a variety of cancer biomarkers. Core-shell nanoparticles, consisting of a core material coated with a shell, have shown great potential in biosensing applications for cancer due to their unique physicochemical properties, such as high surface area, tunable optical/electrical properties, and enhanced catalytic activity, which can significantly improve the sensitivity, selectivity, and stability of biosensors. Various synthetic approaches, such as sol-gel, hydrothermal, co-precipitation, seed-mediated growth, solvothermal, reverse microemulsion, layer-by-layer assembly, and electrochemical deposition, can be employed to fabricate core-shell nanostructures with tailored properties for biosensing applications, and the choice of core and shell materials, as well as the fabrication method, can be optimized to enhance the biorecognition, transduction, and signal amplification capabilities of the biosensor. This chapter will provide a comprehensive overview of the diverse biosensing techniques for cancer detection, the role of core-shell nanostructures in improving biosensing performance, and the strategies for the efficient fabrication of core-shell nanoconstructs for enhanced cancer biosensing applications.