This review highlights the significance of key tumor suppressor genes, including TP53, CDKN2A, SMAD4, and KRAS, in pancreatic cancer. Each gene's role, prevalence, and impact on tumor development and progression are analyzed, emphasizing the complex molecular landscape of pancreatic cancer. The review also underscores the prognostic value of specific mutations, such as loss of TP53, and explores potential targeted therapies based on these molecular signatures. Genomic analyses are crucial for risk assessment, early detection, and personalized treatment approaches in pancreatic cancer. Overall, the findings provide a comprehensive understanding of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.This review highlights the significance of key tumor suppressor genes, including TP53, CDKN2A, SMAD4, and KRAS, in pancreatic cancer. Each gene's role, prevalence, and impact on tumor development and progression are analyzed, emphasizing the complex molecular landscape of pancreatic cancer. The review also underscores the prognostic value of specific mutations, such as loss of TP53, and explores potential targeted therapies based on these molecular signatures. Genomic analyses are crucial for risk assessment, early detection, and personalized treatment approaches in pancreatic cancer. Overall, the findings provide a comprehensive understanding of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.