Climate change is a major concern because of its potential effects on biodiversity and the agricultural sector. The domesticated sunflower, Helianthus annuus L., is the fourth most important oilseed crop in the world [1], is cultivated as hybrids and is promising for agriculture adaptation because it can maintain stable yields across a wide variety of environmental conditions, especially during drought stress [2]. To highlight the molecular processes related to the drought adaptation strategies, we studied the responses of eight parental lines (four males and four females) and their 16 hybrids cultivated on the outdoor high-throughput automated phenotyping platform Heliaphen [3] where two water regimes were implemented and ecophysiological traits were measured. Leaf samples from 144 samples were collected for multi-omics analyses including label-free shotgun analysis and protein identification and quantification. Statistical learning methods without a priori allowed us to reduce this complex molecular system [4] and to model proteomics and phenomics relationships to identify molecular players of heterotic behaviors and their roles during drought stress. We showed dramatic behavioral differences between hybrids and parental lines with solid interaction with water deficit that are exemplified by some highly interesting protein candidates. Further analysis of these genes or proteins highlights the impact of genetic variation on regulatory networks that could be selected to improve heterotic groups and breed for drought stress tolerance. Current integration of eco-physiological, proteomics, transcriptomics and metabolomics levels in order to achieve a more holistic view will be presented and discussed.