Pancreatic cancer is a highly lethal malignant tumor characterized by challenges in early diagnosis and limited therapeutic options, leading to an exceptionally low clinical cure rate. With the advent of novel cancer treatment paradigms, ferroptosis-a form of iron-dependent regulated cell death driven by lipid peroxidation-has emerged as a promising therapeutic strategy, particularly for tumors harboring mutations. However, the poor bioavailability and insufficient tumor-targeting capabilities of conventional drugs constrain the efficacy of ferroptosis-based therapies. Recent advancements in nanotechnology and imaging-guided treatments offer transformative solutions through targeted drug delivery, real-time monitoring of treatment efficacy, and multimodal synergistic strategies. This article aims to elucidate the mechanisms underlying ferroptosis in pancreatic cancer and to summarize the latest identified therapeutic targets for ferroptosis in this context. Furthermore, it reviews the recent progress in nanotechnology-based ferroptosis therapy for pancreatic cancer, encompassing ferroptosis monotherapy, synergistic ferroptosis therapy, and endogenous ferroptosis therapy. Subsequently, the integration of imaging-guided nanotechnology in ferroptosis therapy is summarized. Finally, this paper discusses innovative strategies, such as stroma-targeted ferroptosis therapy, immune-ferroptosis synergy, and AI-driven nanomedicine development, offering new insights and directions for future research in pancreatic cancer treatment.