Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements. Increasing researches focus on the identification of somatic mutations and other genetic aberrations that drive pancreatic cancer has led to a new era of precision medicine based on molecular subtyping. However, few known molecular classifications are used to guide clinical strategies. Specific scientific, regulatory and ethical challenges must be overcome before genomic and transcriptomic discoveries can be translated into the clinic.