The global increase in extreme weather and climate events may dramatically impact agriculture, food safety, and socioeconomic dynamics. The Mediterranean basin is already exposed to extreme climatic events, severely challenging viticulture, a pivotal Mediterranean agro–industry. This study aims to understand better how climate is expected to evolve in six viticulturally important Mediterranean regions in Portugal, Italy, Turkey and Morocco, using a 4–member ensemble of climatic model projections under Representative Concentration Pathways (RCP) 4.5 and 8.5 for 2041–2070, and using the 1981–2010 period as a baseline. By comparing the main specific challenges these locations will face, we comparatively define the best strategies to reduce the impacts of climate change at the national and regional levels. Projections show increases in overall temperatures, up to + 3.6°C than the historical baseline, whilst precipitation projections indicate decreases that could reach 36% of the overall annual precipitation. Biological effective degree days, consecutive dry days, growing season length, tropical nights, or very heavy precipitation days, also show challenging prospects for viticulture in these countries. A screening of the adaptative strategies already undertaken in the studied countries suggests that growers are taking reactive rather than preventive strategies. Moreover, the discussion of the most suitable strategies in this study is region–specific, i.e., prioritised by the specific needs of each location. The conclusions drawn herein may support local growers, improving their decision–making based on the most adequate adaptive strategies to their conditions, thus optimising their sustainable production under changing climates.