Climate change’s current and future scenarios strongly influence plant growth and yield. Desert lands already have the most severe environmental conditions, such as heat, salinity, and drought on the earth and recent abrupt climatic disasters lead to increased global desertification. Deserts with harsh conditions of arid terrain forced the plants to develop novel adaptive mechanisms to survive. Such conditions provide an exceptional opportunity to study the adaptation mechanisms, and its genetic basis that can help understanding plants’ secrets to withstand climate change. Genome sequencing of desert plants can strengthen our interpretation on physiological and biochemical mechanisms, helping to identify genetic sequences crucial for climate change adaptation. Also, transcriptome profiling and metabolomics reveal actively expressed genes and secondary metabolites under various stress conditions. These molecular insights contribute to accumulate valuable information about the plants’ resilience to environmental stresses and assist in illustrating the genetic architecture and regulatory networks, mostly relevant for evolution driven by climate change. Further, these steps assure interventions of new strategies to support programs for enhancing food security. In this review chapter, we describe the morphological, anatomical, physiological, biochemical, and genetic features of desert plants and discuss the basic genetic mechanism behind their systemic adjustments to harsh climatic conditions. The chapter highlighted how desert plants can be a good source of help for plants affected by climate change. This knowledge can be transferred to crop plants, enhancing their ability to withstand harsh environments and reducing crop loss.