Background Tenebrionidae (Insecta: Coleoptera) are a conspicuous component of desert fauna worldwide. In these ecosystems, they are significantly responsible for nutrient cycling and show remarkable morphological and physiological adaptations. Nevertheless, Tenebrionidae colonizing individual deserts have repeatedly emerged from different lineages. The goal of our study was to gain insights into the phylogenetic relationships of the tenebrionid genera from the Atacama Desert and how these taxa are related to the globally distributed Tenebrionidae. Methods We used newly generated transcriptome data (47 tribes, 7 of 11 subfamilies) that allowed for a comprehensive phylogenomic analysis of the tenebrionid fauna of this hyperarid desert and fills a gap in our knowledge of the highly diversified Tenebrionidae. We examined two independent data sets known to be suitable for phylogenomic reconstructions. One is based on 35 neuropeptide precursors, the other on 1,742 orthologous genes shared among Coleoptera. Results The majority of Atacama genera are placed into three groups, two of which belong to typical South American lineages within the Pimeliinae. While the data support the monophyly of the Physogasterini, Nycteliini and Scotobiini, this does not hold for the Atacama genera of Edrotini, Epitragini, Evaniosomini, Praociini, Stenosini, Thinobatini, and Trilobocarini. A suggested very close relationship of Psammetichus with the Mediterranean Leptoderis also could not be confirmed. We also provide hints regarding the phylogenetic relationships of the Caenocrypticini, which occur both in South America and southern Africa. Apart from the focus on the Tenebrionidae from the Atacama Desert, we found a striking synapomorphy grouping Alleculinae, Blaptinae, Diaperinae, Stenochinae, and several taxa of Tenebrioninae, but not Tenebrio and Tribolium . This character, an insertion in the myosuppressin gene, defines a higher-level monophyletic group within the Tenebrionidae. Conclusion Transcriptome data allow a comprehensive phylogenomic analysis of the tenebrionid fauna of the Atacama Desert, which represents one of the seven major endemic tribal areas in the world for Tenebrionidae. Most Atacama genera could be placed in three lineages typical of South America; monophyly is not supported for several tribes based on molecular data, suggesting that a detailed systematic revision of several groups is necessary.