Abstract 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.