Heat stress is one of the major threats to wheat production in many wheat-growing areas of the world as it causes severe yield loss at the reproductive stage. In the current study, 28 crosses were developed using 11 parental lines, including 7 female lines and 4 male testers following line × tester matting design in 2018–2019. Twenty-eight crosses along with their 11 parental lines were sown in a randomized complete block design in triplicate under optimal and heat stress conditions. Fifteen different morpho-physiological and grain quality parameters were recorded at different growth stages. Analysis of variance illustrated the presence of highly significant differences among wheat genotypes for all traits under both optimal and heat stress conditions. The results of combining ability unveiled the predominant role of non-additive gene action in the inheritance of almost all the studied traits under both conditions. Among parents, 3 parental lines WL-27, WT-39, and WL-57 showed good combining ability under both normal and heat stress conditions. Among crosses, WL-8 × WT-17, WL-37 × WT-17, WL-7 × WT-39, and WL-37 × WT-39 portrayed the highest specific combining ability effects for grain yield and its related traits under optimal as well as heat stress conditions. Biplot and cluster analysis confirmed the results of general and specific combining ability by showing that these wheat crosses belonged to a highly productive and heat tolerant cluster. Correlation analysis revealed a significantly positive correlation of grain yield with net photosynthetic rate, thousand-grain rate, and the number of grains per spike. The designated parental lines and their crosses were selected for future breeding programs in the development of heat resilient, climate-smart wheat genotypes.