Abstract: The construction of human settlements plays a vital role in achieving sustainable development goals. With the growing population, both urban and rural planning—as well as the development of human settlements—on the Qinghai-Tibet Plateau in China have received increasing attention. This study proposed a comprehensive framework to assess the quality of human settlements and identify their limiting factors of Nyingchi City, southeastern Qinghai-Tibet Plateau of China. The framework integrated a region-specific evaluation system tailored to the plateau’s unique characteristics and utilized multi-source data collected through field-based questionnaires and remote sensing. Analytical methods employed include the Criteria Importance Through Intercriteria Correlation (CRITIC) weighting method, difference analysis for evaluating spatial and categorical variations, and a novel approach introduced in this study for identifying limiting factors. In August 2021, a questionnaire-based survey was conducted in the southeastern Qinghai-Tibet Plateau, yielding 823 valid responses. The average evaluation score for human settlement quality (HSQ) was (6.96 ± 0.94), indicating that settlement conditions were approaching the satisfaction threshold. Notably, the score for the health dimension was (6.28 ± 1.41), reflecting relatively underdeveloped health services in the region. From the perspective of spatial patterns, despite its favorable natural conditions, the HSQ in Medog County was relatively backward, reflecting uncoordinated development that warrants attention. Significant differences were observed in the perceptions of human settlements among different groups in terms of ethnicity, income, and educational background. Low ratings for income and employment conditions represented a major limitation to the local HSQ. The development of human settlements in the southeastern Qinghai-Tibet Plateau still needs further promotion due to population disparities and the challenges of creating a healthy environment in high-altitude regions. The results are valuable for improving human settlements in plateau regions, which can help make targeted policy recommendations.