Medial tibial stress syndrome (MTSS) is a common pathology in physically active people and one of many overuse leg injuries present in weight bearing athletes, with the highest prevalence in runners. Researchers have extensively explored treatment for MTSS, but a long-lasting and effective treatment option has not been established. This case report aimed to explore the effects of The MyoKinesthetic System TM (MYK), a form of manual therapy, on two athletes diagnosed with MTSS. Patient one is a 19-year-old male rugby player with a previous history of MTSS, who reported leg pain while running which progressed to constant pain. Patient two is a 24-year-old female collegiate soccer patient who reported increasing leg pain while running, with no previous history of MTSS. After being diagnosed with MTSS, both patients' posture was evaluated using the MYK postural analysis to identify and treat the primary nerve root dysfunction (i.e., S1). Each patient received a total of six MYK treatment sessions over a two-week period. Treatment included manual stimulation via tactile feedback of each muscle innervated by the primary dysfunctional nerve root. Treatments were performed bilaterally with alternating patterns of 4-10 passive and active movements. Implementation of manual therapy resulted in long-term, full resolution of symptoms without modifying or restricting athletic participation. Both patients reported a decrease in pain and an increase in function across six treatment sessions without curtailing activity. Manual therapy techniques such as MYK may be a suitable treatment option for physically active patients with MTSS. The outcomes of this case report suggest that MYK may help improve and ultimately resolve MTSS pain and dysfunction in patients involved in weight bearing physical activity. Future studies should continue to examine the effectiveness of these techniques via randomized clinical trials.