Plants acclimate to the changing environmental conditions by adjusting their molecular responses at different molecular levels including genome, epigenome, transcriptome, metabolome, and proteome levels to ensure survival. Plants adapt to abiotic stresses by establishing a ‘stress memory’ of previous exposures to mild stresses. Stress memory helps plants to develop tolerance and survive recurring exposures to the stress conditions. This memory establishes a new cellular state that differs from the state of unexposed naïve plants. This process is known as priming. Priming and the stress memory give the plants the possibility to acclimate to different biotic and abiotic stress conditions. The acquisition and maintenance of the stress-memory are two separate processes and crucial for successful tolerance to subsequent stress conditions. Priming promises to improve plant performance under severe stress conditions and enhance food production. Therefore, understanding the molecular basis of heat stress priming and stress-induced memory is of vital importance to plant biology. In this thesis, I investigated the role of transcriptional, post-transcriptional and metabolomic regulation controlling plant responses to heat stress, one of the major abiotic stresses affecting agriculture. I designed and established a heat stress priming strategy which reveals that heat stress-induced priming leads to the establishment of heat stress memory that permits plants to survive lethal temperatures. In this thesis, I analyzed the genome-wide differential gene expression, the alternative splicing patterns and regulation, and the reprogramming of the metabolic homeostasis that reprogram the establishment of the heat stress priming and stress-memory. I identified a set of candidate genes and metabolites playing key roles in the establishment of heat stress-induced memory. Intriguingly, it was possible also to establish a link between alternative splicing patterns and heat stress-induced memory. Subsequently, the knowledge of heat stress priming in Arabidopsis was translated into tomato crop plants, to improve their heat stress tolerance. This work enhances our understanding of the molecular basis of heat stress priming, and the establishment of heat stress memory, at transcriptional, post-transcriptional, and metabolomic levels. These findings can be translated into crop species to improve their survival under recurring heat stress conditions to improve world agriculture and food security.