Acute pancreatitis (AP) is a common and life-threatening digestive disorder. However, its diagnosis and treatment are still impeded by our limited understanding of its etiology, pathogenesis, and clinical manifestations, as well as by the available detection methods. Fortunately, the progress of microenvironment-targeted nanoplatforms has shown their remarkable potential to change the status quo. The pancreatic inflammatory microenvironment is typically characterized by low pH, abundant reactive oxygen species (ROS) and enzymes, overproduction of inflammatory cells, and hypoxia, which exacerbate the pathological development of AP but also provide potential targeting sites for nanoagents to achieve early diagnosis and treatment. This review elaborates the various potential targets of the inflammatory microenvironment of AP and summarizes in detail the prospects for the development and application of functional nanomaterials for specific targets. Additionally, it presents the challenges and future trends to develop multifunctional targeted nanomaterials for the early diagnosis and effective treatment of AP, providing a valuable reference for future research.