Mononuclear phagocytes (MPs), which consist of dendritic cells, monocytes, and macrophages, are distributed throughout the body and actively eliminate invading microorganisms and abnormal cells. Depending on the local microenvironment, MPs manifest considerably various lifespans and phenotypes to maintain tissue homeostasis. Vascular-associated mononuclear phagocytes (VaMPs) are the special subsets of MPs that are localized either within the lumen side or on the apical surface of vessels, acting as the critical sentinels to recognize and defend against disseminated tumor cells. In this review, we introduce three major types of VaMPs, patrolling monocytes, Kupffer cells, and perivascular macrophages, and discuss their emerging roles in immunosurveillance during incipient metastasis. We also explore the roles of lineage-determining transcription factors and cell surface receptors that endow VaMPs with potent anti-tumor activity. Finally, we highlight the molecular and cellular mechanisms that drive the phenotypic plasticity of VaMPs and summarize combinatory strategies for targeting VaMPs in overt metastasis.