Despite the progress in pancreatic cancer (PC) chemo/radiotherapies, immunotherapies, and novel targeted therapies and the improvement in its peri-operative management policies, it still has a dismal catastrophic prognosis due to delayed detection, early neural and vascular invasions, early micro-metastatic spread, tumour heterogeneities, drug resistance either intrinsic or acquired, unique desmoplastic stroma, and tumour microenvironment (TME). Understanding tumour pathogenesis at the detailed genetic/epigenetic/metabolic/molecular levels as well as studying the tumour risk factors and its known precancerous lesions aggressively is required for getting a more successful therapy for this challenging tumour. For a better outcome of this catastrophic tumour, it should be diagnosed early and treated through multidisciplinary teams of surgeons, gastroenterologists/interventional upper endoscopists, medical/radiation oncologists, diagnostic/intervention radiologists, and pathologists at high-volume centres. Moreover, surgical resection with a negative margin (R0) is the only cure for it. In this chapter; we discuss the recently updated knowledge of PC pathogenesis, risk factors, and precancerous lesions as well as its different management tools (i.e. surgery, chemo/radiotherapies, immunotherapies, novel targeted therapies, local ablative therapies, etc.).