Perineural invasion (PNI) is a hallmark of pancreatic ductal adenocarcinoma (PDAC), where cancer cells infiltrate and migrate along nerves, contributing to the malignancy’s aggressiveness and poor prognosis. PNI involves the intricate interaction between tumor cells and the neural microenvironment, with nerve growth factor (NGF) playing a pivotal role. NGF binds to TrkA receptors on both primary tumor cells and nerves, driving the infiltration of cancer cells into nerve sheaths and promoting their migration through nerves. This study presents a mathematical model that captures these complex dynamics, illustrating how primary tumor cells initially proliferate, leading to elevated NGF levels. This increase in NGF stimulates a phenotypic shift in tumor cells, enhancing their invasiveness and promoting nerve infiltration. As the tumor invades, nerve density increases, further amplifying NGF levels and supporting a feedback loop that drives continued tumor progression. The model supports the “go or grow” hypothesis, showing how tumor cells transition from a proliferative to an invasive phenotype as they interact with nerves. Our findings underscore the critical role of NGF and nerve density in PNI, providing valuable insights into the tumor-nerve interplay and offering a framework for potential therapeutic interventions targeting this interaction in PDAC.