<p>Cancer remains a leading cause of mortality worldwide, necessitating advances in diagnostic technologies to improve early detection and patient outcomes. Traditional methods such as imaging and biopsy are effective and widely used clinically but are often limited by invasiveness, high cost, and lack of sensitivity for early-stage cancer. In response, biosensors have emerged as promising tools capable of detecting cancer-associated biomarkers including circulating tumor DNA, microRNAs, exosomes, and tumor-associated proteins. These devices are noninvasive, rapid, highly sensitive, and offer real-time monitoring capabilities. This review bridges engineering principles with clinical readiness, covering basic principles, material advances, and evidence supporting clinical use across electrochemical, optical, piezoelectric, and field-effect transistor (FET)-based biosensors. We highlight recent breakthroughs in nanomaterials, amplification strategies, device miniaturization, and wearable biosensor platforms. Despite their advances, current biosensors face challenges in terms of sensitivity, nonspecific binding and signal drift, standardization, manufacturing scalability, production costs, regulatory validation and real-world reproducibility, which restrict their widespread clinical application. This review also discusses the integration between biosensors, artificial intelligence, and liquid biopsy workflows that could pave the way for point-of-care testing and personalized cancer management.</p>