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Even in 21st century, >90% cancer-associated deaths are caused by metastatic disease. Circulating tumor cells (CTCs), which circulate in the blood stream after release from primary tumors, extravasate and form fatal metastases in different organs. Several clinical trials indicate that CTCs can be used as a liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition (EMT), oncologists continue to face enormous challenges in using CTCs as a true “liquid biopsy” for cancer patients. Recent advancements in nanoscience allow us to design nano-architectures with the capability of targeted CTCs isolation and identification. In the current review, we discuss contribution from different groups on the development of graphene oxide based nanoarchitecture for effective isolation and accurate identification of CTCs from whole blood. In the last few years, using zero-dimensional (0D), two dimensional (2D) and three dimensional (3D) multifunctional hybrid graphene oxide (GO), different types of nanoarchitectures have been designed. These nanoarchitectures represent a highly powerful platform for CTC diagnosis. We discuss the major design criteria that have been used to develop hybrid GO nanoarchitectures for selective capture and accurate identification of heterogeneous CTCs from whole blood. At the end, we conclude with the promises, major challenges, and prospect to clinically translate the identification of CTCs using GO based nanotechnology.Graphene oxide based nano-architecture for selective separation of CTCs from blood sample and CTCs identification using multicolor fluorescence and SERS.