Recent evidence shows that interactions between tumor cells, immune cells, and extracellular matrix (ECM) proteins in the stroma play an important role in prostate cancer (PCa) progression. However, to date these factors are not accounted for in clinical evaluation of PCa patients. Our team has developed methods based on matrix-assisted laser desorption/ionization (MALDI) imaging to identify sets of ECM glycan and collagen molecules associated with PCa. In this study, we leverage computational imaging methods and pathomic textural features to assess the potential of MALDI imaging to guide the identification of regions in PCa hematoxylin and eosin stain (H&E) images as tumor or non-tumor. We provide preliminary evidence that MALDI imaging can elucidate tissue properties and guide pathomic textural analysis in H&E images, with potential applications in treatment guidance and prognostication of PCa.