Glioblastoma are notoriously aggressive, malignant primary brain tumors that have variable response to treatment. This presentation will focus on the integrative role of 1) biological sex-differences, 2) heterogeneity in drug-delivery and 3) intra-tumoral molecular diversity (revealed by radiomics) in capturing and predicting this variable response to treatment. Specifically, I will highlight burgeoning insights into sex differences in tumor incidence, outcomes, propensity and response to therapy. I will further, quantify the degree to which heterogeneity in drug delivery, even for drugs that are able to bypass the blood-brain barrier, contributes to differences in treatment response. Lastly, I will propose an integrative role for spatially resolved MRI-based radiomics models to reveal the intra-tumoral biological heterogeneity that can be used to guide treatment targeting and management. [-]