In the relentless pursuit of innovative diagnostic tools for cancer, this review illuminates the cutting-edge realm of extracellular vesicles (EVs) and their biomolecular cargo detection through advanced optical biosensing techniques with a primary emphasis on their significance in cancer diagnosis. From the sophisticated domain of nanomaterials to the precision of surface plasmon resonance, we herein examine the diverse universe of optical biosensors, emphasizing their specified applications in cancer diagnosis. Exploring and understanding the details of EVs, we present innovative applications of enhancing and blending signals, going beyond the limits to sharpen our ability to sense and distinguish with greater sensitivity and specificity. Our special focus on cancer diagnosis underscores the transformative potential of optical biosensors in early detection and personalized medicine. This review aims to help guide researchers, clinicians, and enthusiasts into the captivating domain where light meets cellular secrets, creating innovative opportunities in cancer diagnostics.