Circulating tumor cells (CTCs) shed from the primary tumor mass and circulating in the bloodstream of patients are believed to be vital to understand of cancer metastasis and progression. Capture and release of CTCs for further enumeration and molecular characterization holds the key for early cancer diagnosis, prognosis and therapy evaluation. However, detection of CTCs is challenging due to their rarity, heterogeneity and the increasing demand of viable CTCs for downstream biological analysis. Nanotopographic biomaterial-based microfluidic systems are emerging as promising tools for CTC capture with improved capture efficiency, purity, throughput and retrieval of viable CTCs. This review offers a brief overview of the recent advances in this field, including CTC detection technologies based on nanotopographic biomaterials and relevant nanofabrication methods. Additionally, the possible intracellular mechanisms of the intrinsic nanotopography sensitive responses that lead to the enhanced CTC capture are explored.