This work revealed associations between MRI-derived habitats and oncogenic molecular mechanisms in patients with GBM. The analytical framework and workflow demonstrated in this study are inherently scalable to any number of MR sequences. The four MRI sequences used, FLAIR, T1, T1+C, and T2, are readily available on most modern scanners and used routinely in clinical practice. More advanced sequences such as susceptibility-weighted imaging, diffusion-weighted imaging, or MRI spectroscopy could be incorporated into this framework in a fairly linear manner (with ‘k’ MR sequences, you have 2k habitats). Furthermore, with appropriate imaging and tumor segmentation, this workflow could accommodate data from other tumor types and/or other anatomical sites.