A method and system for estimating physiological heart measurements from medical images and clinical data disclosed. A patient-specific anatomical model of the heart is generated from medical image data of the patient. A patient-specific multi-physics computational heart model is generated based on the patient-specific anatomical model by personalizing parameters of a cardiac electrophysiology model, a cardiac biomechanics model, and a cardiac hemodynamics model based on medical image data and clinical measurements of the patient. Cardiac function of the patient is simulated using the patient-specific multi-physics computational heart model. The parameters can be personalized by inverse problem algorithms based on forward model simulations or the parameters can be personalized using a machine-learning based statistical model.