Pancreatic cancer (PC) is one of the most fatal solid tumors, resulting in more than 250,000 deaths per year globally. It is the eighth leading cause of death from cancer in men and women throughout the world and is now third leading cause of cancer-related deaths in the United States. In addition, the worldwide occurrence of PC ranges from 1 to 10 cases per 100,000 people, indicating a higher incidence in developed countries. Most patients with locally advanced or metastatic disease are not candidates for curative resection due to enormously poor prognosis. Substantial efforts have been taken during the past decade to distinguish better treatments in the absence of efficient screening methods. Regardless of wide-ranging efforts, various systems and therapies have shown insufficient efficacy for PC patients. Therefore, the development of novel drug delivery systems, strategies, and diverse therapeutic approaches to improve the range of active molecules for the treatment of PC is critical. Currently, cancer research focuses on improving the treatment of PC via diverse novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems consist of nanoparticles and liposomes. Strategies or therapeutic approaches intended for PC include radiation therapy, ablation therapy, and gene therapy. These systems and approaches can carry the drug molecules to targeted cancer cells to enhance the effectiveness of tumor penetration. The present review encloses existing novel drug carrier systems and approaches for PC management.