Exosomes have been gaining attention for early cancer diagnosis owing to their biological functions in cells. Several studies have reported the relevance of exosomes in various diseases, including pancreatic cancer, retroperitoneal fibrosis, obesity, neurodegenerative diseases, and atherosclerosis. Particularly, exosomes are regarded as biomarkers for cancer diagnosis and can be detected in biofluids, such as saliva, urine, peritoneal fluid, and blood. Thus, exosomes are advantageous for cancer liquid biopsies as they overcome the current limitations of cancer tissue biopsies. Several studies have reported methods for exosome isolation, and analysis for cancer diagnosis. However, further clinical trials are still required to determine accurate exosome concentration quantification methods. Recently, various biosensors have been developed to detect exosomal biomarkers, including tumor-derived exosomes, nucleic acids, and proteins. Among these, the exact quantification of tumor-derived exosomes is a serious obstacle to the clinical use of liquid biopsies. Precise detection of exosome concentration is difficult because it requires clinical sample pretreatment. To solve this problem, the use of the nanobiohybrid material-based biosensor provides improved sensitivity and selectivity. The present review will discuss recent progress in exosome biosensors consisting of nanomaterials and biomaterial hybrids for electrochemical, electrical, and optical-based biosensors.