Organoids, organ-on-a-chip, and microtumors: Biomimetic 3D tumor models advancing drug development and precision medicine.

The rising global cancer burden underscores the urgent need for more effective drug development and personalized therapies. Conventional screening models, such as 2D cell lines and patient-derived xenografts, fail to adequately recapitulate the architecture, heterogeneity, and microenvironment of human tumors, limiting their clinical translatability. In response, human-derived biomimetic platforms have emerged. Organoids and organ-on-a-chip preserve key tumor genetics and stimulate dynamic, physiologically relevant microenvironments, whereas microtumors are distinguished by high biological fidelity. Microtumors uniquely retain the native tumor ecosystem, capture a broader spectrum of intratumoral heterogeneity, and, critically, maintain a functional immune microenvironment. Together, these systems enable drug screening that more faithfully reflects the clinical context, with strong potential to raise drug development success rates and support individualized therapy. This review consolidates the cutting-edge advancements and critical challenges associated with these models in drug development, precision medicine, and clinical translation. Furthermore, it envisions how Artificial Intelligence (AI) can drive its intelligent evolution, aiming to provide a robust evidentiary basis and practical reference for research and clinical practice, thereby propelling the field of precision oncology into a new era.