Decoding multifactorial stress responses in plants: lessons from omics integration.

Plants in natural and agricultural environments are continuously exposed to multiple simultaneous abiotic stresses whose combined effects markedly differ from those of individual stresses. 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 towards 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 × environment complexity shape plant responses. Together, we propose a roadmap towards a predictive science of plant resilience under MFSC, with direct implications for crop improvement in the context of climate change.