Preserving residual limb health in lower-limb amputees is of paramount significance, given its pivotal role in their overall well-being and mobility. This work reports that the elevated vacuum suspension (EVS) system improves blood hemoglobin oxygenation and reduces the potential risk of limb ischemia compared to the standard-of-care (SOC) socket-liner system via a global oxygen mapping modality of spatial frequency domain imaging (SFDI) to assess skin oxygenation and hemoglobin perfusion qualitatively and quantitatively in individuals with lower-limb loss. Conventional methodologies, such as pulse oximetry, are recognized for their inherent limitations in yielding localized tissue oxygenation measurements, thereby failing to offer a comprehensive evaluation. The introduced imaging modality is postulated to provide a more holistic and detailed analysis of the content of tissue chromophores compared to traditional point measurement techniques. The research protocol enlisted six subjects who participated in a protracted 32-week regimen. This encompassed an array of assessments, including evaluations of limb health, socket fit tests, and surveys gauging the impact of socket pressure on the limb skin, both pre-, and post-physical activity. This study also sought to ascertain the efficacy of an experimental prosthesis incorporating EVS technology, contrasting its performance against standard-of-care prostheses. The findings indicate that compared to SoC, the use of the EVS socket system has benefited the effects of residual limb as measured by improved tissue oxygen and better deeper tissue hemoglobin perfusion. Such insightful data holds substantial promise in aiding clinicians to render more informed decisions about managing individuals with limb loss.