A method and system for non-invasive assessment and therapy planning for coronary artery disease from medical image data of a patient is disclosed. Geometric features representing at least a portion of a coronary artery tree of the patient are extracted from medical image data. Lesions are detected in coronary artery tree of the patient and a hemodynamic quantity of interest is computed at a plurality of points along the coronary artery tree including multiple points within the lesions based on the extracted geometric features using a machine learning model, resulting in an estimated pullback curve for the hemodynamic quantity of interest. Post-treatment values for the hemodynamic quantity of interest are predicted at the plurality of points along the coronary artery tree including the multiple points within the lesions for each of one or more candidate treatment options for the patient, resulting in a respective predicted post-treatment pullback curve for the hemodynamic quantity of interest for each of the one or more candidate treatment options. A visualization of a treatment prediction for at least one of the candidate treatment options is displayed.