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Summary Myrothamnus flabellifoliais a dioecious resurrection plant endemic to southern Africa that has become an important model for understanding desiccation tolerance. Despite its ecological and medicinal significance, genomic and transcriptomic resources for the species are limited.We generated a chromosome‐level, haplotype‐resolved reference genome assembly and annotation forM. flabellifoliaand conducted transcriptomic profiling across a natural dehydration–rehydration time course in the field. Genome architecture and sex determination were characterized, and co‐expression network andcis‐regulatory element (CRE) enrichment analyses were used to investigate dynamic responses to desiccation.The 1.28‐Gb genome exhibits unusually consistent chromatin architecture with unique chromosome organization across highly divergent haplotypes. We identified an XY sexual system with a small sex‐determining region on Chromosome 8. Transcriptomic responses varied with dehydration severity, pointing to early suppression of growth, progressive activation of protective mechanisms, and subsequent return to homeostasis upon rehydration. Late embryogenesis abundant and early light‐induced protein transcripts were dynamically regulated and showed enrichment of abscisic acid and stress‐responsive CREs pointing toward conserved responses.Together, this study provides foundational resources for understanding the genomic architecture and reproductive biology ofM. flabellifoliaand offers new insights into the mechanisms of desiccation tolerance.