Cancer is a complicated disease. Globally, it is one of the major causes for morbidity and mortality. A critical challenge associated with it is the difficulty to accurately diagnose it at an early stage. The malignancy due to multistage and heterogeneity that result from genetic and epigenetic modifications poses critical challenge to diagnose and monitor the progress at an early stage. Current diagnostic techniques normally suggest invasive biopsy procedure that can cause further infections and bleeding. Therefore, noninvasive diagnostic methods with high accuracy, safety and earliest detection are the needs of the hour. Herein, we provide a detailed review on the advanced methodologies and protocols developed for the detection of cancer biomarkers based on proteins, nucleic acids and extracellular vesicles. Furthermore, existing challenges and the improvements essential for the rapid, sensitive and noninvasive detection have also been discussed.