The relationship between permafrost conditions and the distribution of infrastructure in the Usa Basin, Northeast European Russia, is analyzed. About 75% of the Basin is underlain by permafrost terrain with various degrees of continuity (isolated patches to continuous permafrost). The region has a high level of urban and industrial development (e.g., towns, coal mines, hydrocarbon extraction sites, railway, pipelines). GIS-analyses indicate that about 60% of all infrastructure is located in the ‘high risk’ permafrost area, here defined as the zones of isolated to discontinuous permafrost (3–90% coverage) with ‘warm’ ground temperatures (0 to −2°C). Ground monitoring, aerial photo interpretation, and permafrost modeling suggest a differential response to future global warming. Most of the permafrost-affected terrain will likely start to thaw within a few decades to a century. This forecast poses serious challenges to permafrost engineering and calls for long-term investments in adequate infrastructure that will pay back over time.