Many types of disease can be treated with ablation, a medical procedure which applies energy to destroy small regions of tissue that do not behave normally. Ablation therapy can be used to treat conditions like arthritis, uterine fibroids, and cancer. It can also treat disruptions of the heart’s regular rhythm, such as atrial fibrillation. Ablation procedures can be difficult to perform, and sometimes multiple treatments may be necessary. A deeper understanding of exactly how the settings associated with the ablation procedure affect the biological tissue could lead to better results. This project aims to improve the understanding of radiofrequency ablation’s interactions with heart tissue through a combination of theory, multi-physics and machine-learning models, and experiments. To ensure the experiments reflect the differences in tissue structures and properties of real patients, tissue from human hearts no longer needed after being replaced by transplants will be used when possible. Medical doctors will help assess the practical significance of the project’s results. This study has the potential to lead to improved ablation treatments and patient outcomes, and the new methodology can be extended, with minor adaptations, to other types of diseases. Educational components include training of graduate and undergraduate students, contributions to undergraduate and graduate courses, and engagement of the general public with interactive programs available through a website.