Models of CTC invasion, cluster formation, intravasation, and induction of tumor metastasis are crucial in understanding cancer progression. The immune suppressive tumor microenvironment, along with stromal cells such as CAFs at the primary site, play significant role in promoting tumorigenesis. In tumors prone to metastasis, EMT allows single CTCs to detach from the primary tumor lesion. This is followed by the upregulation of stemness factors (OCT4, NANOG, SOX2), ECM remodeling, and upregulation of cell–cell interaction mediators, all of which support collective invasion and migration of tumor cells. After intravasation, platelets and neutrophils provide cluster survival against shear stress and antitumor immune cells such as T and NK cells. Following CTC extravasation and dissemination to distant organs, they may enter a dormant phase for an unknown period or induce micro and macro colonization, ultimately leading to tumor metastasis. Abbreviations: CAF, cancer-associated fibroblasts; CTC, circulating tumor cell; DTCs, disseminated tumor cells; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; VEGF, vascular endothelial growth factor; TAM, tumor-associated macrophages; Treg, regulatory T cell