Abstract: Frequent changes in global climate enhance environmental cues, threaten agricultural systems, which jeopardizes food security, and impair the achievements of the United Nations Sustainable Development Goal 2 “Zero Hunger”. To achieve a sustainable path, use of biostimulants represents a new strategy to enhance plant resilience against abiotic stresses like drought, temperature, salt, waterlogging, and heavy metals. This review explores recent developments in biostimulant technologies, aiming to clarify the processes that underlie their ability to promote plant tolerance. We also highlight the versatile roles of small RNA, peptides, and hormones as emerging molecular regulators, thereby revealing their potential for use as natural biostimulants. Developing on this, transformative effects of microbial biostimulants that use microbiota to strongly regulate plant stress-responsive modules are explored. Furthermore, AI-driven early warning systems provide the opportunity to identify timely stress responses, thus enabling the discovery of multi-omics network modules, allowing rational biostimulant design. These findings are then used to guide the metabolic engineering of tailored biostimulants, where the identified key regulators and network modules become direct targets for formulation or synthetic biology approaches. This review defines a roadmap for crop stress tolerance by clarifying the mechanisms of rationally designed biostimulants, thereby paving the way for climate-resilient agriculture and sustainable food systems.

Key words: artificial intelligence, climate change, metabolic engineering, multi‐omics integration, natural and synthetic biostimulants, SMART crops