Nesterenkonia sp. AN1 is a polyextremophile isolated from Antarctic desert soil. Genomic analyses and genome comparisons with three mesophilic Nesterenkonia strains indicated that the unique genome fraction of Nesterenkonia sp. AN1 contains adaptive features implicated in the response to cold stress including modulation of membrane fluidity as well as response to cold-associated osmotic and oxidative stress. The core genome also encodes a number of putative cold stress response proteins. RNA-Seq-based transcriptome analyses of Nesterenkonia sp. AN1 grown at 5 ºC and 21oC showed that there was significant induction of transcripts that code for antioxidants at 5 ºC, demonstrated by the upregulation of sodA, bcp and bpoA2. There was also overexpression of universal stress protein genes related to uspA, along with genes encoding other characterised cold stress features. Genes encoding the two key enzymes of the glyoxylate cycle, isocitrate lyase (ICL) and malate synthase (AceB) were induced at 5 ºC, suggesting possible adaptation strategies for energy metabolism in cold habitats. These genomic features may contribute to the survival of Nesterenkonia sp. AN1 in arid Antarctic soils.