<p>Triploid oysters are valued in aquaculture for their rapid growth and sterility. In recent years, Pacific oyster (<i>Crassostrea gigas</i>) autotriploids suffer high summer mortality in northern China, while allotriploids between male tetraploid <i>C. gigas</i> and female diploid <i>C. angulata</i> exhibit greater resilience. High temperature and low salinity are critical environmental stressors driving summer mass mortality in oysters. Their combined functions impose more severe physiological challenges than either stress alone. This study compared the survival rates and molecular responses of autotriploid and allotriploid oysters exposed to combined temperature (22, 26, and 30 °C) and salinity (16, 23, and 30) stresses. Under the most severe stress condition (30 °C, salinity 16), the activities of antioxidant enzymes (SOD, CAT), levels of lipid peroxidation (MDA), the expressions of genes involved in metabolism (<i>HK, PK, SDH, CS</i>, and <i>Na</i>⁺/<i>K</i>⁺-<i>ATPase</i>), genes related to apoptosis (<i>Bcl-2, Bax</i>), and heat shock proteins (<i>Hsp70, Hsp90</i>) were analyzed. Allotriploids showed significantly higher survival rates, stronger antioxidant capacity, reduced oxidative damage, and a lower apoptotic index (<i>Bax/Bcl-2</i> ratio) compared to autotriploids. Moreover, allotriploids exhibited earlier and more pronounced upregulation of key genes related to energy metabolism and heat shock proteins. These findings reveal the mechanism of the superior tolerance of allotriploid oysters to combined effects of heat and hypo-saline, which is attributed to enhanced aerobic metabolism, antioxidant defense, apoptosis resistance, and <i>Hsp</i> regulation.</p>