Heat stress has severe impacts on rabbit performance because they have difficulty getting rid of excess heat. The interaction between genetic and environmental factors plays a vital role in the adaptation process. The current study aimed to evaluate the effects of interaction between the genotype and heat conditions (G×H) on litter size and growth traits. Two rabbit lines were used in the current study, Egyptian maternal line (APRI) and New Zealand White (NZW). The rabbits were raised under normal (22°C) or heat stress (35°C) conditions. The does were raised in individual cages, and their kits were reared under the same conditions. Negative effects of heat conditions were noted for litter traits, as heat stress had significantly reduced the number of born alive, total born, and marketed number rabbits by about 16, 11, and 25%, respectively. Moreover, growth traits were reduced under heat stress conditions compared to normal temperature conditions. Significant differences between genotypes were observed, APRI rabbits were higher than NWZ rabbits in the total born, number of born alive, number weaned, and the number of marketed rabbits by 10, 8, 11, and 10%, respectively. Genotype by heat conditions interaction effects were observed, APRI litters under normal conditions showed significantly higher litter traits than NWZ litters, whereas relevant reductions in litter traits of APRI line than NZW litters when reared in heat conditions. For growth traits, the differences between the two lines under normal conditions were reduced when animals of the two lines were raised under heat stress, for BW28, BW42, BW63, ADG28−42, and DF28−42 while these differences were increased for ADG42−63, DF28−42 and feed conversion during the whole fattening period. Based on the observed G × H interactions, it is important to select the animals under the same production conditions to raise rabbits that can cope with the expected global warming conditions.