Qinghai-Tibet Plateau (QTP) is the largest permafrost region among middle- and low-latitude regions in the world. Permafrost in QTP is dominated by unstable and climate-driven. It is especially vulnerable to climate change and ecosystem disturbances (both natural and human). Currently, more than 9389 km of roads, 580 km of railways, 2631 km of power lines, and 1064590 m² of buildings are located in the QTP permafrost area. Depending on altitude, the warming rate of the QTP has been twice the global average in recent decades and in the foreseeable future. Climate change-induced permafrost degradation can seriously threaten the stability of infrastructure and thus increase the infrastructure repair and replacement frequency. The consequence can be expressed as the shortening of useful life and increases maintenance costs, leading to diverse financial risks. The damage to infrastructure caused by near-surface permafrost degradation is directly related to the well-being of 10 million people and the sustainable development on the Qinghai-Tibet Plateau, the Third Pole of the Earth. Here we identify the economic damage caused by permafrost degradation to infrastructure on the Qinghai-Tibet Plateau by integrating data-driven projection, multihazard index, and lifespan replacement model. We found that additional cost of approximately $6.31 billion will be needed to maintain the service function of current infrastructure under the historical scenario (SSP245) by 2090. While 20.9% of these potential costs can be saved with strategic adaptations. Controlling global warming to below 1.5 °C will reduce the costs by $1.32 billion relative to the 2 °C target of Paris Agreement. These findings highlight the importance of mitigating global warming and of investment in the adaptation and maintenance of infrastructure on the Qinghai-Tibet Plateau, which has a sparse population but is a climate hotspot.