Plants in their physical environment face multiple biotic and abiotic stresses during their life cycle. In nature, environmental stresses often co-occur – such as water deficit and nutrient deficiencies – and can have synergistic, antagonistic or additive effects on the plant molecular responses. In pea (Pisum sativum), combination of water stress (WS) and sulfur (S) deficiency showed a mitigation effect on the seed protein composition, as compared to S deficiency occurring alone (Henriet et al., 2019). To better understand how pea responds to WS and/or S deficiency, a multi-omics (transcriptomics, proteomics, metabolomics, ionomics) analysis has been performed from leaf samples collected during a time course, on different lots of plants subjected to either WS, S deficiency, or to the combination of the two stressors. Our analyses revealed that 21% of the stress-responsive mRNAs, proteins, metabolites and ions showed a stronger response when S deficiency occurs with WS, suggesting synergistic or additive effects. Using a weighted-gene co-expression network approach, we evidenced genes strongly regulated by changes in the S concentration in leaves. The comparison between our transcriptomics and proteomics data allows us to formulate hypotheses on the level of regulation (transcriptional or post-transcriptional) of these genes. We also propose candidate genes that might help plants to better tolerate combinatorial stresses.