Environments often vary across a life cycle, imposing fluctuating natural selection across development. Such fluctuating selection can drive evolutionary responses specific to distinct life-history stages. However, selection and genetic variation, phenotypic plasticity, and their interaction (GxE), as well as genetic correlation across development dictate stage-specific evolution. Thus, quantifying genetic covariance of fitness-related traits and plasticity across development is vital to determine whether stage-specific adaptation occurs in nature. Additionally, the interaction of genetic variation and environmental plasticity (GxE) may be stage-specific, leading to a 3-way interaction between genotype, environment, and development or GxDxE. To test for these patterns in a natural system, we exposed larvae and adults of Drosophila melanogaster isogenic lines derived from a natural population to extreme heat and cold after developmental acclimation to cool (18°C) and warm (25°C) conditions and measured genetic variance for thermal hardiness. We detected significant GxE that was specific to larvae and adults for cold and heat hardiness (GxDxE), but no significant genetic correlation across development for either trait at either acclimation temperature. However, cross-development phenotypic correlations for acclimation responses suggest that plasticity itself may be developmentally constrained, though rigorously testing this hypothesis requires more experimentation. In general, we find evidence for thermal niche adaptation across development as larvae are more heat-hardy while adults are more cold-hardy. These results illustrate the potential for stage-specific adaptation within a complex life cycle and highlight the importance of measuring traits at appropriate developmental stages and environmental conditions when predicting evolutionary responses to changing climates.