Pancreatic cancer presents significant challenges due to low early diagnosis rates, ineffective drug treatments, and drug resistance, innovative foundational therapies for pancreatic cancer still face numerous obstacles in transitioning from trials to widespread clinical application. This article systematically outlines the key challenges across multiple dimensions, including molecular subtypes of pancreatic cancer, tumor microenvironment, preclinical models, early detection, treatment strategies, and research translation. It proposes potential breakthrough directions: early screening and improved diagnostic efficiency; personalized treatment plans based on genetic profiling of patients; development of more relevant preclinical research models; optimization of multimodal treatment strategies; and enhanced efficiency in translating basic research to clinical applications. Among these areas, the lag in early screening along with insufficient precision in personalized treatment, represent the core focal points for current breakthroughs. Promoting collaborative innovation across four key dimensions of “model systems, diagnostic tools, treatment strategies, and clinical trial design”, can bring hope for prolonging the survival of patients with pancreatic cancer.