Repositioning old drugs in combination with clinical standard chemotherapeutics opens a promising clinical treatment approach for patients with pancreatic cancer. This review highlights gemcitabine treatment along with the therapeutic repositioning of continuous perfusion of aspirin and oseltamivir phosphate as an efficacious treatment option for individuals affected by pancreatic cancer. The data suggest that repurposing these drugs with continuous perfusion with gemcitabine (GEM) hinders chemoresistance, tumor progression, epithelial-mesenchymal transition (EMT) program, metastases, and cancer stem cells in a mouse model of human pancreatic cancer. These encouraging findings merit further exploration to evaluate the possibility of applying these treatments in a clinical context, aiming to enhance the prognosis of cancer patients facing an otherwise fatal disease.