<p>Despite significant advancements, cancer is still a major cause of death worldwide, in part because it is often diagnosed late and conventional diagnostic tools such as blood tests are not sensitive enough for cancer detection. The tremendous sensitivity, label-free detection, miniaturization, and real-time detection capabilities have made optical fiber biosensors an attractive diagnostic platform. In this systematic review, recent developments in optical fiber biosensors for cancer biomarker detection are critically analyzed based on analytical performance, biosensing architecture, and translational potential. According to the guidelines of PRISMA 2020, a thorough search in PubMed, Scopus, Web of Science, IEEE Xplore, ScienceDirect, and Google Scholar revealed 25 relevant studies from 2016 to 2026. The studies included multiple cancers, such as breast, lung, prostate, thyroid, ovarian, and colorectal cancers, and targeted important biomarkers, including HER2, CEA, PSA, CD44, miRNA-21, and CA125. Optical fiber biosensor platforms were surface plasmon resonance (SPR)-based sensors, tilted fiber Bragg gratings (TFBGs), Fabry–Perot interferometers, microfiber couplers, and nanomaterial sensors. The results show that the analytical sensitivity of modern optical fiber biosensors is extremely high, and detection limits can often be as low as femtomolar to attomolar by integrating nanomaterials and using interferometric enhancement techniques. In spite of these developments, the studies are mostly proof-of-concept and are not widely clinically validated and rely on buffer or spiked bio-samples. Reproducibility, biofouling, and lack of standardization between platforms are major hurdles. Overall, optical fiber biosensors show great promise for the next decade of cancer diagnostics, especially in the field of liquid biopsy, yet they have not been thoroughly validated clinically and integrated into routine diagnostic workflow.</p> Graphical abstract <p></p>