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Despite this, our mechanistic understanding of plant stress biology still largely relies on reductionist frameworks based on single or pairwise interactions. Here, we argue that plant responses to increasing stress complexity are fundamentally non-additive and involve emergent molecular, metabolic, and physiological states that require a shift toward integrative and predictive approaches. We synthesize recent advances showing how signaling and metabolic networks are rewired under multifactorial stress combination (MFSC), leading to nonlinear behaviors and context-dependent regulation. We highlight the central role of multi-omics integration in uncovering system-level responses and discuss how emerging computational frameworks, including machine learning, can transform high-dimensional datasets into predictive models linking molecular states to plant performance. We further evaluate the limitations of current experimental systems, emphasizing the gap between controlled-environment studies and field conditions, where stress dynamics, microbiome interactions, and genotype\u00d7environment complexity shape plant responses. Together, we propose a roadmap toward a predictive science of plant resilience under MFSC, with direct implications for crop improvement in the context of climate change.<\/jats:p>","DOI":"10.1093\/jxb\/erag389","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:44:54Z","timestamp":1785498294000},"source":"Crossref","is-referenced-by-count":0,"title":["Decoding multifactorial stress responses in plants: lessons from omics integration"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7522-3493","authenticated-orcid":false,"given":"Laia","family":"Molinero-Domingo","sequence":"first","affiliation":[{"name":"Department of Biology, Biochemistry and Environmental Sciences, University Jaume I , Castell\u00f3 de la Plana 12071 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-8443","authenticated-orcid":false,"given":"Lidia S","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Biology, Biochemistry and Environmental Sciences, University Jaume I , Castell\u00f3 de la Plana 12071 ,","place":["Spain"]},{"name":"The Division of Plant Sciences Technology, Interdisciplinary Plant Group, College of Agriculture, Food and Natural Resources, Christopher S. Bond Life Sciences Center, University of Missouri , 1201 Rollins St, Columbia, MO 65201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-0241","authenticated-orcid":false,"given":"Rosa M","family":"Rivero","sequence":"additional","affiliation":[{"name":"Department of Plant Nutrition, Centro de Edafolog\u00eda y Biolog\u00eda Aplicada del Segura (CEBAS)\u2013CSIC , Murcia 30100 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3192-7450","authenticated-orcid":false,"given":"Ron","family":"Mittler","sequence":"additional","affiliation":[{"name":"The Division of Plant Sciences Technology, Interdisciplinary Plant Group, College of Agriculture, Food and Natural Resources, Christopher S. Bond Life Sciences Center, University of Missouri , 1201 Rollins St, Columbia, MO 65201 ,","place":["USA"]},{"name":"Advanced Agriculture Initiative, Tel-Hai University of Kiryat Shamona and the Galilee , Kiryat Shamona 1220800 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-9371","authenticated-orcid":false,"given":"Sara I","family":"Zandalinas","sequence":"additional","affiliation":[{"name":"Department of Biology, Biochemistry and Environmental Sciences, University Jaume I , Castell\u00f3 de la Plana 12071 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026091607513527500_erag389-B1","doi-asserted-by":"crossref","first-page":"kiaf006","DOI":"10.1093\/plphys\/kiaf006","article-title":"How plants adapt to combined and sequential abiotic stresses: a transcriptomics 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