Pancreatic cancer, a highly fatal malignancy, is predicted to rank as the second leading cause of cancer-related death in the next decade. This highlights the urgent need for new insights into personalized diagnosis and treatment. Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics, few known molecular classifications are translated to guide clinical strategies and require a paradigm shift. Notably, chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics, proteomics, metabonomics, and metagenomics. Therefore, a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential therapeutic options. In this review, we recapitulated the molecular spectrum from different omics levels, discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact, and proposed some methodological and scientific challenges in store.