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Computational tools are beginning to enable patient-specific surgical planning to localize and prescribe thermal dosing for liver cancer ablation therapy. Tissue-specific factors (e.g., tissue perfusion, material properties, disease state, etc.) have been found to affect ablative therapies, but current thermal dosing guidance practices do not account for these differences. Computational modeling of ablation procedures can integrate these sources of patient specificity to guide therapy planning and delivery. This paper establishes an imaging-data-driven framework for patient-specific biophysical modeling to predict ablation extents in livers with varying fat content in the context of microwave ablation (MWA) therapy. Patient anatomic scans were segmented to develop customized three-dimensional computational biophysical models and mDIXON fat-quantification images were acquired and analyzed to establish fat content and determine biophysical properties. Simulated patient-specific microwave ablations of tumor and healthy tissue were performed at four levels of fatty liver disease. Ablation models with greater fat content demonstrated significantly larger treatment volumes compared to livers with less severe disease states. More specifically, the results indicated an eightfold larger difference in necrotic volumes with fatty livers vs. the effects from the presence of more conductive tumor tissue. Additionally, the evolution of necrotic volume formation as a function of the thermal dose was influenced by the presence of a tumor. Fat quantification imaging showed multi-valued spatially heterogeneous distributions of fat deposition, even within their respective disease classifications (e.g., low, mild, moderate, high-fat). Altogether, the results suggest that clinical fatty liver disease levels can affect MWA, and that fat-quantitative imaging data may improve patient specificity for this treatment modality. [ABSTRACT FROM AUTHOR]