The hypoxic tumor microenvironment is a critical driver of pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. However, a comprehensive, multi-omics resource systematically profiling the molecular alterations induced by chronic hypoxia across diverse cellular components of PDAC is currently lacking. Here, we present a deeply characterized dataset generated from three PDAC cell lines, one pancreatic stellate cell line, and one normal pancreatic ductal epithelial cell line cultured under normoxic and chronic hypoxic (1% O₂) conditions. The dataset includes matched transcriptomic (RNA-Seq), proteomic, and phosphoproteomic profiles from biologically triplicated samples, all supported by phenotypic validation data confirming hypoxia-induced proliferation and gemcitabine resistance.