Pancreatic cancer (PC) is a highly malignant digestive system tumor with extremely high mortality and recurrence rates. While traditional surgical resection and chemotherapy remain the main treatment options, challenges such as high postoperative recurrence and poor prognosis persist. Therefore, exploring more effective comprehensive treatment strategies is crucial for improving patient survival and prognosis. This review systematically summarizes recent advances in systemic therapy for PC, with a focus on the application and efficacy of chemotherapy, targeted therapy, and immunotherapy. Additionally, it discusses the potential of neoadjuvant therapy, integrated traditional Chinese and Western medicine approaches, and conversion therapy in enhancing the effects of conventional chemotherapy. Studies have shown that targeted therapy can enhance antigen presentation and reduce side effects, while immune checkpoint inhibitors, cancer vaccines, and adoptive cell immunotherapy help mitigate tumor immune evasion and improve the tumor microenvironment. Despite continuous innovation in treatment approaches, clinical management of PC, particularly for advanced-stage patients, still faces significant challenges. Future research should focus on early diagnosis, precision medicine, and personalized treatment strategies to further improve cure rates and patient survival quality, providing more effective therapeutic options for clinical practice.