BACKGROUND: This study is designed to explore the prognostic significance of exosome-related genes (ERGs) and their impact on the the tumor microenvironment (TME) of pancreatic cancer. METHODS: Transcriptomic data alongside clinical details of patients with PC were retrieved from both The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) repository. A collection of 121 exosome-associated genes were obtained from the ExoBCD database. For constructing a risk scoring model, the absolute shrinkage and selection operator (LASSO) regression method was employed. Gene set enrichment and variance analyses were facilitated by the clusterProfiler and GSVA R software tools. Additionally, CIBERSORT was used to estimate immune cell infiltration levels. Lastly, the TIDE algorithm was leveraged to evaluate the connection between gene expression and drug sensitivity. A series of experiments were used to verify the role of DLGAP5 in PC. RESULTS: Two unique molecular clusters were uncovered, and our analysis revealed a connection between ERG dysregulation across multiple layers and patient demographic, histopathological attributes, prognosis, as well as immune cell infiltration patterns within the TME. An ERG_score was developed for forecasting overall survival and its predictive capacity was confirmed in PC cases. A precise nomogram was established to enhance the clinical utility of the ERG_score. Patients in the low-risk group exhibited higher immune and ESTIMATE scores than that in the high-risk group, displaying an improved overall survival (OS). The ERG_score was associated with cancer stem cell (CSC) index and drug sensitivity. Crucial evaluations of ERGs illuminated the significance of DLGAP5, emphasizing its expression in PC and its contributory role in tumor growth stimulation. CONCLUSIONS: Our investigation reveals a correlation between the exosome-related risk assessment signature and the survival outcome as well as immune cell infiltration in patients with PC. This finding potentially paves the way for enhanced therapeutic strategies for PC.