Tumor marker detection plays a critical role in early cancer screening, therapeutic evaluation, and recurrence prediction. However, conventional detection methods are constrained by inadequate sensitivity and specificity, limiting their utility in precision diagnosis. The emergence of nanobiosensors offers a promising alternative. This review systematically summarizes recent advances in nanobiosensors for tumor marker detection, with a focus on functionalized nanoprobe design and signal transduction technologies. On this basis, the key bottlenecks hindering clinical translation, including biofouling in complex biological matrices, batch-to-batch reproducibility, and the lack of standardized validation protocols are critically analyzed. Potential solutions are discussed, such as anti-fouling nanointerfaces, artificial intelligence-assisted multi-target analysis, and wearable monitoring. This review aims to provide a reference for the iterative advancement of precision diagnostic technologies for cancer.
