Metastasis is the leading cause of death in cancer patients because of the difficulty to treat the secondary tumors and the latency period between dissemination of metastatic cells from the primary tumor to other sites and clinical detection. As such, metastasis accounts for a considerable bulk of the $100 billion yearly cost of cancer medical treatment. Understanding the mechanisms underlying metastasis events could have an enormous impact on patient survival rates and how clinicians and scientists target drugs to reduce metastasis. Targeting CTCs has garnered much attention as a therapeutic target in recent years. They are a bottleneck in the progressive stages of metastasis. My thesis explores how circulating tumor cells interact with the host environment and the host innate immune response that ensues. There are two host environments that I investigate 1) blood circulation where circulating tumor cells come in contact with white blood cells and 2) the inflammatory cells in a secondary organ, in this case the brain. My methods include extensive use of transgenic animal models, two-photon microscopy, bioluminescence imaging and imaging analysis. The work presented in this dissertation contributes information about how the innate immune system can be used as a therapeutic drug carrier to target CTCs.