Malignant tumours represent a significant public health issue posing a grave threat to human life and health, garnering considerable attention in the field of biomedical science in recent years. Early screening and diagnosis of tumours provide patients with valuable treatment time, constituting a crucial measure in tumour prevention and management. Surface-enhanced Raman spectroscopy (SERS), with its advantages of ultra-high sensitivity, high precision, and multiplexing capabilities, has been widely applied in the detection of tumour markers. This paper examines SERS-based biosensors for three distinct tumour markers: prostate-specific antigen (PSA) for prostate cancer screening, alpha-fetoprotein (AFP) for primary liver cancer detection, and chromogranin A (CgA) for neuroendocrine tumour diagnosis. Compared to SERS technology, alternative early-stage tumour marker detection methods—such as chemiluminescent immunoassays, enzyme-linked immunosorbent assays, and real-time quantitative PCR—face limitations in widespread clinical adoption due to their higher costs, longer analysis times, and greater operational complexity. To address current clinical application challenges, future advancements in SERS-based biosensor detection of tumour markers will primarily be achieved through innovative improvements to the biosensor substrate.