Sesuvium portulacastrum, a facultative edible halophyte, is characterized by a remarkable molecular and physiological adaptability, making it an ideal system for studying plant resilience under environmental stress. The ability of S. portulacastrum to cope with salt stress attributed to a variety of physiological, biochemical, and molecular mechanisms. One key strategy involves the compartmentalization of sodium ions (Na+) in vacuoles, which helps maintain osmotic balance and prevent cellular damage under saline conditions. The plant maintains osmotic balance through the compartmentalization of Na+ in vacuoles, a process facilitated by Na+/H+ antiporters (NHX) and salt overly sensitive 1 (SOS1) genes. Additionally, high-affinity K+ transporters (HKTs) regulate K+ and Na+ ion homeostasis. Besides these, the differential expression of calcium signaling-related genes, transporter genes, transcription factors, and lipid synthesis-related genes also play a vital role in the salt adaptation mechanism. Investigations into the genetic and molecular cues of salt tolerance in S. portulacastrum are essential, particularly as global climate change exacerbates environmental stressors. This chapter explores the use of transcriptomic and genomic tools to uncover the specific genes involved in salt tolerance, offering valuable insights for developing crops better suited to saline environments.