Metastasis stands to remain as the primary challenge in managing patients outcome. In recent years, research has shifted toward cancer stem cells (CSCs) and their impact on metastasis, more specifically how CSCs exist, their interactions with the surrounding environment, and their pathogenesis. CSCs are of great interest due to their ability to self-renew, obtain invasive properties, aggressively disseminate, and mature in a heterogenous manner. Understanding CSCs have shed a new light on molecular factors that could potentially be targeted to identify metastatic cells early with the hope of intervention. While research in the field of metastatic cancer stem cells (MCSCs) is early, this chapter aims to discuss the current understanding of CSCs’ role in metastasis and provide an overview of the underlying processes, more specifically the role of the CSCs, primary tumor niche, epithelial-to-mesenchymal transition (EMT), pre-metastatic niche, metastatic niche, mesenchymal-to-epithelial transition (MET), angiogene-sis, and dormancy in relation to metastasis. This chapter also explores potential molecular markers that could increase the metastatic potential of CSCs in common cancers, including colorectal, breast, pancreatic, glioblastoma, and lung cancers.