Recent research has highlighted the crucial role of the nervous system in the development and spread of cancer. Studies on pancreatic cancer have mapped the changes in nerve connections within organs as the disease progresses. These studies reveal that different types of nerve cells, each with distinct chemical and functional properties, undergo significant modifications. Some nerve cells begin remodeling their connections during the precancerous stage, while others actively invade fully developed tumors. Experimental nerve ablation studies support the idea that the initial neuronal response may be tumor-suppressive, with subsequent events attracting protumorigenic nerves. We are beginning to uncover the signals and mechanisms driving these changes, including the reactivation of pathways that guide axon growth during development, the activation of repair programs in supportive glial cells, and alterations in the mechanical properties of the tumor microenvironment. These findings underscore the critical role of nerve plasticity in the progression of pancreatic cancer.