Abstract: Pancreatic cancer is the third leading cause of cancer‑related death in the world due to its high malignancy, difficult in early diagnosis, poor treatment efficacy, and high mortality. In recent years, benefiting from the progress of combined chemotherapy and neoadjuvant therapy, the prognosis of patients with pancreatic cancer has been improved to a certain extent. However, compared with other tumors, progress of precision medicine in pancreatic cancer is slow. The authors introduce the latest progress and difficulties in precision medicine of pancreatic cancer including molecular classification based on single gene and omics, monitoring tumor progression and guide treatment by minimally invasive liquid biopsy, as well as targeting therapy and immuno-therapy, in order to accelerate the development of precision medicine of pancreatic cancer.