Pancreatic ductal adenocarcinoma (PDAC) ranks among the leading causes of cancer-related deaths worldwide. Despite advances in precision oncology in other malignancies, treatment of PDAC still largely relies on conventional chemotherapy. Given the dismal prognosis and heterogeneity in PDAC, there is an urgent need for personalized therapeutic strategies to improve treatment response. Organoids, generated from patients' tumor tissue, have emerged as a powerful tool in cancer research. These three-dimensional models faithfully recapitulate the morphological and genetic features of the parental tumor and retain patient-specific heterogeneity. This review summarizes existing precision oncology approaches in PDAC, explores current applications and limitations of organoid cultures in personalized medicine, details preclinical studies correlating in vitro organoid prediction and patient treatment response, and provides an overview of ongoing organoid-based clinical trials.