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Nucleotide metabolism significantly influences tumor cell proliferation, yet its specific profile in pancreatic cancer remains inadequately understood. This study was aimed at characterizing the nucleotide metabolic profile in pancreatic cancer and assessing the contribution of the key gene adenylate kinase (AK) 4. Multiomics data, including transcriptomic, single-cell sequencing, spatial transcriptomic, and metabolomics datasets, were obtained from publicly accessible platforms. The impact of AK4, a key gene of nucleotide metabolism, on the proliferation and migration of pancreatic cancer cells was investigated using various molecular biological techniques. Nucleotide pathway-related metabolites exhibited marked differences in abundance between pancreatic cancer tissues and normal pancreatic tissues. Single-cell sequencing analysis identified MKI67⁺ and myeloid cells as subsets with overactive nucleotide metabolism. Immune cells from tumor tissues had a higher score of nucleotide metabolism than those from the normal pancreas. Spatial transcriptomics revealed spatial features of nucleotide metabolism in pancreatic cancer. Pancreatic cancer patients displayed distinct clinical heterogeneity in nucleotide metabolism, with elevated nucleotide signaling correlating with poorer patient prognosis. Furthermore, tumor subtypes showed variations in immune microenvironment features and immune checkpoint expression, which may explain their differential prognoses. A nucleotide metabolic-derived prognostic panel had the potential to predict the clinical outcomes of patients with pancreatic cancer. The AK4 gene played a central role in nucleotide metabolism, and its overexpression in clinical pancreatic cancer samples was frequently linked to adverse patient outcomes. Cell-based experiments revealed that AK4 knockdown suppressed pancreatic cancer cell proliferation and migration. Abnormal nucleotide metabolism pathways are implicated in pancreatic cancer onset and progression.