Nowadays, a biotechnological game changer in regenerative medicine and regenerative pharmacology is indisputably induced pluripotent stem cell technology. Particularly, human-induced pluripotent stem cells (hiPSCs) construct the basis of various functional models in both health and disease states. Undifferentiated, like their natural embryonic counterparts’ human embryonic stem cells (hESCs), hiPSCs represent a model for pluripotency and self-renewal. Once differentiated, hiPSCs give rise to endoderm, mesoderm and ectoderm, and produce numerous cell lineages derived from these three germ layers. Thereby, hiPSCs provide a robust system to recapitulate the development that naturally occurs in the human embryo. These cells provide an effective platform to produce disease-specific target cells. These remarks have far-reaching implications to study the congenital dysfunction in monogenic and multifactorial diseases to reproduce in vitro pathophysiology of such diseases. The advent of three-dimensional (3D) biofabrication strategies combined with human pluripotent stem cells has also opened the door to a better understanding of mechanisms of pancreas development and pathophysiology of pancreatic congenital abnormalities and both endocrine and exocrine pancreas diseases. The possibility of obtaining pancreatic ductal epithelial cells from patient-derived hiPSCs improved our ability to recapitulate in vitro the complex pathophysiology of several pancreatic diseases, such as the life-threatening pancreatic ductal adenocarcinoma, chronic pancreatitis leading to permanent pancreas damage, pancreatic cystic fibrosis and cystic fibrosis-related diabetes. Herein, it was discussed how integration of human-induced pluripotent stem cell technology and 3D bioprinting employed “organ-on-a-chip” devices emerged as a guiding tool precisely offering clues of human ductal epithelial pancreas diseases with their potentials establishing rich pipelines for biopharmaceutical innovations, large-scale toxicology testing and next frontier of precision medical therapies.