The standard pre-clinical tissue models have limited versatility and accuracy, which are inadequate to recapitulate complex biological diseases. Two-dimensional cultured cancer cell lines and animal models can poorly recapitulate the patient-specific diseased tissue, often limiting drug testing and hampering further development. Awareness of these limitations has resulted in recent ongoing efforts toward the development of three-dimensional (3D) disease models. Current research focuses on designing physiologically relevant 3D models that offer numerous advantages, particularly in the tailored design of patient-specific drugs and individualized clinical treatments. We are advancing beyond animal model-based pre-clinical testing, with the need for new modeling approaches aided by the technological advances in 3D bioprinting and biofabrication. The synergistic efforts of tissue bioengineering and regenerative medicine, supported by novel biofabrication approaches, hold the key to unlocking further advancements in disease modeling, paving the way for personalized therapies and patient-specific treatments.