This research manuscript explores the integration of advanced technologies in organoid engineering for personalized precision medicine. The study delves into mechanobiological modulation, ultrasound stimulation, and acoustofluidics to enhance organoid engineering. It focuses on developing organoids-on-a-chip platforms with integrated biosensors for real-time monitoring, improving disease modeling, and drug testing. The manuscript addresses challenges and opportunities in large-scale organoid manufacturing, emphasizing scalability and reproducibility. Key topics include the role of mechanobiology in tissue development and disease, therapeutic ultrasound applications, and the potential of organ-on-a-chip technology in drug development and toxicology. The research also examines stem cell therapy, tumor growth, and the extracellular matrix's impact on cell behavior. The manuscript aims to contribute to the advancement of 3D tissue models, microphysiological systems, and multi-organoid systems, offering a comprehensive perspective on the potential of these technologies in personalized medicine.This research manuscript explores the integration of advanced technologies in organoid engineering for personalized precision medicine. The study delves into mechanobiological modulation, ultrasound stimulation, and acoustofluidics to enhance organoid engineering. It focuses on developing organoids-on-a-chip platforms with integrated biosensors for real-time monitoring, improving disease modeling, and drug testing. The manuscript addresses challenges and opportunities in large-scale organoid manufacturing, emphasizing scalability and reproducibility. Key topics include the role of mechanobiology in tissue development and disease, therapeutic ultrasound applications, and the potential of organ-on-a-chip technology in drug development and toxicology. The research also examines stem cell therapy, tumor growth, and the extracellular matrix's impact on cell behavior. The manuscript aims to contribute to the advancement of 3D tissue models, microphysiological systems, and multi-organoid systems, offering a comprehensive perspective on the potential of these technologies in personalized medicine.