Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. While the immune and vascular systems have been described as having robust influences on cancer, a growing body of evidences points to the role of the nervous system in promoting cancer development. Our laboratory ( Science 12 July 2013: Vol. 341 no. 6142 ) uncovered that sympathetic and parasympathetic nerve fibers from the autonomic nervous system (ANS) infiltrate prostate tumors and contribute to the early stages of cancer development as well as tumor invasion and metastasis. We have now characterized the process of neo-neurogenesis in primary tumors and metastasis. Doublecortine (DCX+) neural progenitors leave the subventricular zone, a neurogenic niche in the brain, and circulate through the blood to home into primary tumor and metastasis where they can differentiate into adrenergic neurons to sustain early stages of tumor development (Nature 15 May 2019: advance online publication). The nervous system interacts with the immune and vascular systems to maintain homeostasis in the brain and peripheral organs. Therefore, we are conducting additional studies to further characterize a neurogenic, immune and vascular interactome in the brain and in tumors involved in controlling cancer development. Understanding biological systems or pathways that might be regulated by the central or peripheral nervous system in tumors will be pivotal to developing novel cancer therapies.