Pancreatic cancer remains a highly lethal malignancy with a poor prognosis due to late-stage diagnosis and limited therapeutic options. The identification of reliable biomarkers is crucial for enhancing early detection, prognostic evaluation, and targeted treatment. MicroRNAs (miRNAs) have emerged as promising candidates for pancreatic cancer biomarkers. This review explores the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. The authors discuss the latest advancements in omics data-driven biomarker discovery and perform a case study using public datasets to address research discrepancies, challenges, and limitations. They also present analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, offering new insights into identifying robust miRNA-centric biomarkers. The review highlights the potential of exosomal miRNAs as non-invasive biomarkers for early detection and the importance of combining multiple miRNAs or other molecules to enhance diagnostic accuracy. Additionally, it discusses the therapeutic implications of miRNAs in pancreatic cancer, including their potential as targeted therapies. Despite the promising findings, several challenges, such as standardization of methods and the need for large-scale datasets, must be addressed to fully realize the clinical potential of miRNAs in pancreatic cancer management.Pancreatic cancer remains a highly lethal malignancy with a poor prognosis due to late-stage diagnosis and limited therapeutic options. The identification of reliable biomarkers is crucial for enhancing early detection, prognostic evaluation, and targeted treatment. MicroRNAs (miRNAs) have emerged as promising candidates for pancreatic cancer biomarkers. This review explores the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. The authors discuss the latest advancements in omics data-driven biomarker discovery and perform a case study using public datasets to address research discrepancies, challenges, and limitations. They also present analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, offering new insights into identifying robust miRNA-centric biomarkers. The review highlights the potential of exosomal miRNAs as non-invasive biomarkers for early detection and the importance of combining multiple miRNAs or other molecules to enhance diagnostic accuracy. Additionally, it discusses the therapeutic implications of miRNAs in pancreatic cancer, including their potential as targeted therapies. Despite the promising findings, several challenges, such as standardization of methods and the need for large-scale datasets, must be addressed to fully realize the clinical potential of miRNAs in pancreatic cancer management.