Lipolytic enzymes catalyze the hydrolysis and synthesis of ester compounds. They are valuable in the pulp, food, and textile industries. This study aims to comprehensively evaluate the extreme properties of a hormone-sensitive lipase (EstATII-TM) isolated from the Red Sea Atlantis II brine pool. EstATII-TM was cloned, expressed, and its biochemical activities were assessed under different conditions. EstATII-TM catalytic properties and resistance to different metal ions were compared to commercial thermophilic esterases under different temperatures. Phylogenetically, EstATII-TM was assigned to the GDSAG motif subfamily of hormone-sensitive lipase. The optimal enzyme activity was evident at a temperature of 30 °C and pH 7–8. The enzyme retained 84.9% of its activity at 0.5 M NaCl. EstATII-TM maintained 93% to 97% activity at −40 and −20 °C, respectively. EstATII-TM activity was significantly enhanced, up to 10-fold, at temperatures ranging from 45 to 65 °C in the presence of 1 mM Cu²⁺, Cd²⁺, Ba²⁺, Mn²⁺, and Zn²⁺. EstATII-TM showed superior catalytic activity and resistance-to/enhancement-by metal ions compared to two commercial thermophilic esterases. The Red Sea Atlantis II brine EstATII-TM is characterized by tolerance to high temperatures, stability to hot and cold conditions, as well as toxic heavy metal contamination, making it an ideal candidate for industrial processes.