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Difficult to detect early, aggressive tumor biology, and resistance to chemotherapy, radiotherapy, and immunotherapy result in a poor prognosis of pancreatic cancer patients with a 5\u2010year survival of 10%. With advances in cancer nanotechnology, new imaging and drug delivery approaches that allow the development of multifunctional nanotheranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. In this review, we will introduce potential applications of innovative theranostic strategies to address major challenges in the treatment of pancreatic cancer at different disease stages. Several important issues concerning targeted delivery of theranostic nanoparticles and tumor stromal barriers are discussed. We then focus on the development of a magnetic iron oxide nanoparticle platform for multimodal therapy of pancreatic cancer, including MRI monitoring targeted nanoparticle\/drug delivery, therapeutic response, and tumor re\u2010staging, activation of tumor immune response by immunoactivating nanoparticle and magnetic hyperthermia therapy, and intraoperative interventions for improving the outcome of targeted therapy.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>Nanotechnology Approaches to Biology &gt; Nanoscale Systems in Biology<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Therapeutic Approaches and Drug Discovery &gt; Nanomedicine for Oncologic Disease<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Diagnostic Tools &gt; In Vivo Nanodiagnostics and 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