Circulating tumor cells are a hallmark of cancer metastasis which accounts for approximately 90% of all cancer-related deaths. Their detection and characterization have significant implications in cancer biology and clinical practice. However, CTCs are rare cells and consist of heterogeneous subpopulations, requiring highly sensitive and specific techniques to identify and isolate them with high efficiency. Nanomaterials, with unique structural and functional properties, have shown strong promise to meet the challenging demands. In this review, we discuss CTC capture and therapeutic targeting, emphasizing the significance of the nanomaterials being used for this purpose. The next generation of therapy for metastatic cancer may well involve capturing and even directly neutralizing CTCs using nanomaterials.