The use of wild plants is considered to be an eco-friendly and promising natural resource. In sandy desert habitats,Leptadenia pyrotechnicaflourishes as a xerophytic shrub with high biomass production. As a dominant shrub in the arid sand dune habitats of Saudi Arabia,Leptadenia pyrotechnica(Forssk.) Decne (Asclepiadaceae) is one of the most common xerophytes; the many medicinal uses of this plant include treating allergies, productive coughs, abortions, diabetes, stomach disorders, fevers, kidney disorders, and stones. In such a distribution, morpho-anatomical characteristics, among other adaptive traits, play an important role. This study aims to characterize some morpho-anatomical adaptations ofL. pyrotechnicain two stressful habitats: the hyper-arid inland sand dunes of the Empty Quarter (EQ) and the arid coastal sand dunes of Jazan. A morpho-anatomical analysis of plant stems and roots from both habitats was conducted using light microscopy (LM) and scanning electron microscopy (SEM). The outcomes indicated similar characteristics, a low surface-to-volume ratio (S/V), a thin boundary layer (δbl), an epidermis with many layers of hypodermis, bundles of sclerenchymatous cells around vascular tissue, and storage starch grains in ray parenchyma between xylem conduits. On the other hand, theL. pyrotechnicastem from the hyper-arid habitat of the Empty Quarter revealed more encrypted stomata, more elongated palisade cells, less calcium oxalate crystals with low Ca percentage, and a high vulnerability index of xylem vessels compared with the same traits of the stem from the Jazan coastal sand dunes habitat. Roots ofL. pyrotechnicafrom both habitats revealed similar features of general anatomy. However, differences in specific anatomical traits were observed, especially in xylem vessel characters. The vulnerability index of root xylem vessels from the Empty Quarter habitat was more than that from the Jazan coastal sand dunes habitat. Furthermore, vestured bordered pits in root xylem walls were more abundant in the Empty Quarter habitat than in the Jazan coastal sand dunes habitat. As a result, these characteristics in the morpho-anatomy ofL. pyrotechnicafrom both habitats provide practical adaptations to highly stressful conditions, along with specific anatomical traits relating to each habitat.