The purpose of the current case study was to determine the influence of an 8-week home intervention training utilizing a partial hand prosthesis on hemodynamic responses of the brain and gross dexterity in a case participant with congenital unilateral upper-limb reduction deficiency (ULD). The case participant (female, 19 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS) before and after an 8-weeks home intervention training. During baseline, there was a broad cortical activation in the ipsilateral sensorimotor cortex and a non-focalized cortical activation in the contralateral hemisphere, which was non-focalized, while performing a gross manual dexterity task using a prosthesis. After the 8-week home intervention training, however, cortical activation shifted to the contralateral motor cortex while cortical activation was diminished in the ipsilateral hemisphere. Specifically, the oxygenated hemodynamics (HbO) responses increased in the medial aspects of the contralateral primary motor and somatosensory cortices. Thus, these results suggest that an 8-week prosthetic home intervention was able to strengthen contralateral connections in this young adult with congenital partial hand reduction. This was supported by the case participant showing after training an increased flexor tone, increased range of motion of the wrist, and decreased times to complete various gross dexterity tasks. Changes in HbO responses due to the home intervention training follow the mechanisms of use-dependent plasticity and further guide the use of prostheses as a rehabilitation strategy for individuals with ULD.