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Grapevine cultivation, such as the whole horticulture, is currently challenged by several factors, among which the extreme weather events occurring under the climate change scenario are the most relevant. Within this context, the present study aims at characterizing at the berry level the physiological response of Vitis vinifera cv. Sauvignon Blanc to sequential stresses simulated under a semi-controlled environment: flooding at bud-break followed by multiple summer stress (drought plus heatwave) occurring at pre-vèraison. Transcriptomic and metabolomic assessments were performed through RNASeq and NMR, respectively. A comprehensive hormone profiling was also carried out. Results pointed out a different response to the heatwave in the two situations. Flooding caused a developmental advance, determining a different physiological background in the berry, thus affecting its response to the summer stress at both transcriptional levels, with the upregulation of genes involved in oxidative stress responses, and metabolic level, with the increase in osmoprotectants, such as proline and other amino acids. In conclusion, sequential stress, including a flooding event at bud-break followed by a summer heatwave, may impact phenological development and berry ripening, with possible consequences on berry and wine quality. A berry physiological model is presented that may support the development of sustainable vineyard management solutions to improve the water use efficiency and adaptation capacity of actual viticultural systems to future scenarios. [ABSTRACT FROM AUTHOR]