The metastasis in which the cancer cells degrade the extracellular matrix (ECM) and invade to the sur-rounding and far tissues of the body is the leading cause of mortality in cancer patients. With a lot of advancement in the field, yet the biological cause of metastasis are poorly understood. The microfluidic system provides advanced technology to reconstruct a variety of in vivo-like environment for studying the interactions between tumor cells (TCs) and endothelial cells (ECs). This review gives a brief account of both two-dimensional models and three-dimensional microfluidic systems for the analysis of TCs-ECs co-culture as well as their applications to anti-cancer drug screening. Furthermore, the advanced methods for analyzing cell-to-cell interactions at single-cell level were also discussed.