Abstract: A crossbreeding program was established in 2019 to address the declining Crassostrea gigas harvests caused by Pacific Oyster Mortality Syndrome (POMS). As a part of the program, this study was performed to estimate the genetic structure underlying phenotypic variation. Fifteen complete diallel crossings of C. gigas and C. angulata, comprising 60 full-sib families, were used to evaluate the general combining ability (GCA) and specific combining ability (SCA), as well as genotype and environment interactions for shell height (SH), summer survival (SS), and thermal tolerance (TT) of reciprocal hybrids GA (C. gigas ♀ × C. angulata ♂) and AG (C. angulata ♀ × C. gigas ♂) grown in Rongcheng and Rushan, Shandong Province, China. The results suggested that heterosis of the reciprocal hybrids was evident for SH, SS, and TT. The hybrid GA had larger heterosis than AG in both testing environments, and can be a potential donor in the breeding program. The male C. gigas had better GCA for SH in Rongcheng, whereas male C. angulata was a good general combiner for SS and TT in both Rongcheng and Rushan. The estimate of SCA was much higher than GCA for SH and lower than GCA for TT. To harness both additive and non-additive genetic effects, combination breeding could be taken to develop hybrid varieties possessing both thermal tolerance and fast-growing traits. The positive correlations between SH and TT suggested that these traits could be improved simultaneously. The significant G × E interactions demonstrated the importance to undertake site-specific breeding programs in different environments. Overall, this study can provide essential information for developing crossbreeding strategies for the oyster farming industry.