Pancreatic cancer (PC) has a high degree of malignancy and a 5-year survival rate of <10%, with the core molecular mechanisms of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (90%), inactivation of tumor protein p53/cyclin-dependent kinase inhibitor 2A/SMAD family member 4, and epigenetic dysregulation (including DNA methylation and non-coding RNA alterations), which promotes the progression of PC. In recent years, breakthroughs have been made in targeted therapy, including the clinical application of KRASG12C inhibitors (sotorasib, adagrasib) and KRASG12D inhibitors, and the strategies targeting epidermal growth factor receptor, DNA repair (PARP inhibitors), and immune microenvironment (combined therapies targeting PD-1 and PD-L1) have significantly improved the treatment outcome of PC. Nevertheless, drug resistance and tumor heterogeneity remain huge challenges. Precision medicine and combined therapies should be adopted in the future to improve the prognosis of patients.