Pancreatic cancer remains one of the most aggressive malignancies globally, with a 5-year survival rate of less than 13%. This poor prognosis stems from late-stage diagnosis and intrinsic resistance to conventional therapies, including chemotherapy and radiotherapy. A hallmark of PC is oncogene-driven metabolic reprogramming-notably mediated by mutations in KRAS and other key pathways-which fuels tumor progression and undermines the efficacy of neoadjuvant treatments. Consequently, there is a pressing demand for non-invasive techniques capable of mapping metabolic alterations at both the tumor microenvironmental and systemic levels. This review will discuss molecular imaging techniques that identify metabolic changes within the tumor microenvironment. By bridging preclinical insights with clinical applications, we highlight how these innovations promise to revolutionize PC diagnosis, treatment stratification, and therapeutic monitoring, ultimately paving the way for precision oncology.