Pulmonary hypertension imposes a chronic and progressively increasing pressure load on the right ventricle (RV), driving structural and functional remodeling[1]. Although many aspects of myocardial adaptation to mechanical stress have been characterized (e.g., fiber re-orientation[2], fibrosis[3]), these changes are only part of a much larger, multiscale response. Pairing a rodent disease model with a mouse-specific digital twin enables direct mechanistic interrogation of how transcriptional and proteomic programs interact with organ-level biomechanics, which is an especially challenging problem given the tight mechanical coupling between the RV and left ventricle (LV)[4]. We have developed a mouse-specific digital-twin framework that integrates MRI-derived cardiac geometry, biomechanical function, and molecular signaling into a unified multiscale model of RV remodeling induced by pulmonary arterial banding (PAB), with some animals also undergoing transverse aortic constriction (TAC) to assess inter-ventricular dependencies. High-resolution MRI is used to segment each heart, compute regional strain, and construct a 3D finite-element model with spatially varying tissue properties. Each heart also undergoes deep-tissue imaging to quantify fiber orientation, which is incorporated directly into the finite-element mesh. To individualize these models, we solve a large-scale optimization problem that integrates pressure–volume relationships and MRI-derived strain to identify subject-specific biomechanical parameters. To mechanistically connect tissue deformation to molecular remodeling, we integrate molecular signaling pathways, calibrated to single-cell/nuclear RNA-sequencing into the model. Each finite element is assigned both mechanical state variables and a corresponding transcriptomic/proteomic signature, allowing us to evaluate how local stress, strain, and fiber-level mechanics couple to cellular programs that govern tissue remodeling. This integrated imaging-based framework provides a path toward explaining how RV pressure overload induces coordinated changes in structure, mechanics, and gene expression across the heart. It also establishes a foundation for predictive, mechanistically interpretable digital twins capable of projecting disease trajectories and identifying molecular targets strongly influenced by biomechanical load.