Tylosema esculentum, commonly known as marama bean, is an underutilized perennial legume native to arid regions of Southern Africa. A comprehensive overview of the current state of genomic research on marama bean, highlighting its potential as a climate-resilient crop for food security, is provided. The chapter reports the first draft genome assembly of marama bean, a tetraploid with an estimated genome size of 1.1–1.2 Gb, and includes analysis of the nuclear, chloroplast, and mitochondrial genomes that revealed existence of two distinct germplasm types within the species. The genome assembly has enabled the identification of important genes related to nutritional qualities and antinutrients, particularly protease inhibitors. Notably, marama bean exhibits an expansion of the Kunitz-type inhibitor family and a contraction of the Bowman–Birk-type inhibitors compared to other legumes. The chapter also discusses the potential for improving marama bean’s agronomic traits through genomics-assisted breeding and explores its unique adaptations to drought conditions. Overall, this research lays the genomic foundation for further genetic studies and the development of marama bean as a valuable crop for arid regions facing climate change challenges.