Despite extensive research in the pathogenesis, early detection, and therapeutic approaches of pancreatic ductal adenocarcinoma (PDAC), it remains a devastating and incurable disease. As the global incidence and prevalence of PDAC continue to rise, there is a pressing need to place strong emphasis on its prevention. Although it is widely recognized that cigarette smoking, a potentially modifiable risk factor, has been linked to PDAC development, its contribution to prognosis is still uncertain. Moreover, the mechanistic pathways of PDAC progression secondary to smoking are various and lack a summative narration. Herein, we update and summarize the direct and indirect roles cigarette smoking plays on PDAC development, review literature to conclude the impact cigarette smoking has on prognosis, and postulate a comprehensive mechanism for cigarette smoking-induced PDAC.