Systems and methods are disclosed for simulating microvascular networks from a vascular tree model to simulate tissue perfusion under various physiological conditions to guide diagnosis or treatment for cardiovascular disease. One method includes: receiving a patient-specific vascular model of a patient's anatomy, including a vascular network; receiving a patient-specific target tissue model in which a blood supply may be estimated; receiving joint prior information associated with the vascular model and the target tissue model; receiving data related to one or more perfusion characteristics of the target tissue; determining one or more associations between the vascular network of the patient-specific vascular model and one or more perfusion characteristics of the target tissue using the joint prior information; and outputting a vascular tree model that extends to perfusion regions in the target tissue, using the determined associations between the vascular network and the perfusion characteristics.