Rotator cuff (RC) tears are the most common cause of shoulder disability, representing one of the highest days-away-from-work rates compared to other work-related injuries. Chronic, degenerative tears can cause pain, decreased range of motion, and weakness, with more than 50% of cases affecting individuals over 60 years of age. As Americans age, they remain active and contribute to the workforce longer than has been seen previously. Thus, the impact of RC pathology on activities of daily living and work activities is expected to grow. Previous work in the area of rotator cuff tear spans a number of scientific and clinical fields, but the results from each setting do not necessarily translate. Therefore, this necessitates coordinated, multi-faceted research into understanding how and why rotator cuff tendon tears initiate and progress. RC tears can be classified by their depth as either full or partial thickness tears, and previous clinical studies report a higher prevalence of partial thickness rotator cuff tears, though most research has focused on full thickness tears. Partial thickness rotator cuff tears are commonly asymptomatic, but may serve as an early timepoint that allows for improved, early clinical intervention. Therefore, the goal of this work was to develop a framework that collates information from clinical, cadaveric, simulation, and animal settings to quantify the changing mechanical environment surrounding partial rotator cuff tear and guide clinical assessment. In Chapter 2, using a seven degree of freedom glenohumeral testing system, we demonstrated 1) the effect of the rotator cuff muscle activation and 2) the role of negative intraarticular pressure during passive glenohumeral abduction. In Chapter 3, we utilize an adjustable material testing apparatus, biaxial tensile material testing of rotator cuff tendon specimens and material fitting to a hyperelastic, fiber-reinforced constitutive model to validate a specimen-specific finite element model of the rotator cuff. In Chapter 4, we formulate a procedure for evaluating partial rotator cuff tear patient motions that can be used as inputs to the validated finite element model. In Chapter 5, we develop an in-vivo small animal testing apparatus for evaluating the mechanical and biological response of tendon during cyclic loading. Ultimately this work serves as a foundation for a coordinated framework that takes partial rotator cuff tear patient information and provides the clinician with quantified rotator cuff tear progression risk. Futures studies that aim to achieve clinical utility will use this framework in conjunction with clinical insight to achieve clinical translation that reduce pain and loss of function due to rotator cuff tear.