Intratumor heterogeneity is often manifested by vascular compartments with distinct pharmacokinetics that cannot be resolved directly by in vivo dynamic imaging. We developed tissue-specific compartment modeling (TSCM), an unsupervised computational method of deconvolving dynamic imaging series from heterogeneous tumors that can improve vascular phenotyping in many biological contexts. Applying TSCM to dynamic contrast-enhanced MRI of breast cancers revealed characteristic intratumor vascular heterogeneity and therapeutic responses that were otherwise undetectable.