The natural environment provides the geographical foundation for human survival and development; however, its suitability for human settlement in high-altitude regions remains insufficiently addressed. This study focuses on the Tibetan Plateau and proposes a Natural Environment Suitability Index of the Plateau (NESP), designed specifically for high-altitude areas. Using the natural location quotient, we assessed the influence of 9 key environmental factors on settlement suitability. To determine indicator weights objectively and comprehensively, we applied 3 methods: the random forest method, the consulting graded method, and the correlation coefficient method. The results indicate a clear spatial gradient: environmental suitability decreases from east to west as altitude increases. Only about 31% of the plateau is categorized as suitable or very suitable, primarily in low-altitude river valleys, while over 69% is classified as unsuitable or very unsuitable, concentrated in central and western regions. Suitable or very suitable areas are deemed appropriate for regulated human activities under strict environmental protection, while unsuitable or very unsuitable regions should be prioritized for ecological conservation. Based on the NESP, we delineated 11 distinct natural suitability zones across the plateau. This study offers a high-altitude-specific framework for assessing the quality of the natural environment for human settlement, providing a scientific foundation for regional planning, environmental management, and the promotion of Sustainable Development Goals in fragile plateau ecosystems.