Right ventricular (RV) failure is a key contributor to the mortality and morbidity of multiple cardiovascular diseases, including congenital heart failure, left ventricular failure with preserved ejection fraction, and pulmonary hypertension. However, there is a lack of treatment options for RV failure patients, due in large part to the poor understanding of RV pathophysiology. Significant remodeling of the tissue occurs at multiple length scales during disease progression, including microstructural (from intracellular and extracellular components), contractile (from active mechanics of muscle cells), mechanical (from passive mechanics of myocardium tissue), and hemodynamic (from cardiovascular circulation system) factors, all of which result in ultimate alterations in RV organ function. In this chapter, we discuss experimental and computational methods of cell and tissue active and passive mechanics assessments, as well as the current knowledge of the changes of and relation between RV microstructure and mechanics with disease progression. Additionally, we present common approaches to measuring RV organ performance and recent applications of multiscale computational modeling to relate and link multiscale changes in the cardiopulmonary system to RV function. Through the combination of experimental and in silico methods, further development and implementation of multiscale computational framework is necessary to delineate critical factors contributing to RV pathophysiology and elucidate potential therapeutic targets for heart failure patients.