Cancer remains a leading cause of death in the United States and other developed countries. In nearly all cases, the cause of death is related to complications associated with tumor metastasis to distant sites such as the brain, lung, liver, and bone. A central feature of tumor progression is the acquisition of a blood supply, which provides nutrients for the growing tumor as well as conduits for transport of cancer cells. Our understanding of how a tumor acquires and manipulates a blood supply has been gleaned largely from animal models, but more recent advances in tissue engineering and microfabrication have led to clever 3D in vitro models of tumors that include blood vessels. This chapter will first briefly review the process of blood vessel growth including our knowledge of blood vessels within the cancer microenvironment, and discuss the most recent advances to mimic blood vessel growth in the tumor microenvironment using 3D in vitro culture methods. Finally, we discuss several important factors that control blood vessel growth including hypoxia, cellular metabolism, and tissue mechanics, which provide rich opportunities for future investigation.