Rotator cuff (RC) tendinopathy is a common recurrent cause of shoulder pain, and resistance exercise is the first-line recommended intervention. Proposed causal mechanisms of resistance exercise for patients with RC tendinopathy consist of four domains: tendon structure, neuromuscular factors, pain and sensorimotor processing, and psychosocial factors. Tendon structure plays a role in RC tendinopathy, with decreased stiffness, increased thickness, and collagen disorganization. Neuromuscular performance deficits of altered kinematics, muscle activation, and force are present in RC tendinopathy, but advanced methods of assessing muscle performance are needed to fully assess these factors. Psychological factors of depression, anxiety, pain catastrophizing, treatment expectations, and self-efficacy are present and predict patient-reported outcomes. Central nervous system dysfunctions also exist, specifically altered pain and sensorimotor processing. Resisted exercise may normalize these factors, but limited evidence exists to explain the relationship of the four proposed domains to trajectory of recovery and defining persistent deficits limiting outcomes. Clinicians and researchers can use this model to understand how exercise mediates change in patient outcomes, develop subgroups to deliver patient-specific approach for treatment and define metrics to track recovery over time. Supporting evidence is limited, indicating the need for future studies characterizing mechanisms of recovery with exercise for RC tendinopathy.