Assessing the genetic variability of plant performance under heat and drought scenarios can contribute to reduce the negative effects of climate change. We propose here an approach that consisted of (1) clustering time courses of environmental variables simulated by a crop model in current (35 years 3 55 sites) and future conditions into six scenarios of temperature and water deficit as experienced by maize (Zea mays L.) plants; (2) performing 29 field experiments in contrasting conditions across Europe with 244 maize hybrids; (3) assigning individual experiments to scenarios based on environmental conditions as measured in each field experiment; frequencies of temperature scenarios in our experiments corresponded to future heat scenarios (+5°C); (4) analyzing the genetic variation of plant performance for each environmental scenario. Forty-eight quantitative trait loci (QTLs) of yield were identified by association genetics using a multi-environment multi-locus model. Eight and twelve QTLs were associated to tolerances to heat and drought stresses because they were specific to hot and dry scenarios, respectively, with low or even negative allelic effects in favorable scenarios. Twenty-four QTLs improved yield in favorable conditions but showed nonsignificant effects under stress; they were therefore associated with higher sensitivity. Our approach showed a pattern of QTL effects expressed as functions of environmental variables and scenarios, allowing us to suggest hypotheses for mechanisms and candidate genes underlying each QTL. It can be used for assessing the performance of genotypes and the contribution of genomic regions under current and future stress situations and to accelerate breeding for drought-prone environments.With climate changes, crops will be subjected to more frequent episodes of drought and high temperature that may threaten food security (IPCC, 2014). Reducing the impacts of these effects is an urgent priority that (not exclusively) involves the genetic progress of plant performance under heat and drought stresses (Tester and Langridge, 2010;Lobell et al., 2011). Because hundreds of new genotypes of most cereals are commercialized every year, a generic approach is needed to avoid an endless series of experiments assessing the performances of the newly released genotypes. A systematic exploration of the natural genetic diversity used in breeding can provide information usable for large groups of genotypes. This entails the identification, among the thousands of accessions existing in gene banks, of allelic variants exhibiting specific adaptation traits by addressing three questions: (1) Is there a genetic variability for yield and related traits in dry and hot environments? (2) Can this genetic variability be dissected into the effect of genomic regions (quantitative trait loci, QTLs), and (3) have these genomic