Ensuring food security is one of the main challenges related to a growing global population under climate change conditions. The increasing soil salinity levels, drought, heatwaves, and late chilling severely threaten crops and often co-occur in field conditions. This work aims to provide deeper insight into the impact of single vs combined abiotic stresses at the growth, biochemical and photosynthetic levels inArabidopsis thalianaL. By studying single and combined stresses, stress interactions and synergic effects have been highlighted. Lower photosynthetic efficiency was recorded from the beginning in all the conditions that included salinity. Consistently, membrane stability and ROS production, combined with a targeted metabolomic quantification of glycine, GABA, proline, and glycine-betaine molecular markers, highlighted the hierarchically stronger impact of salinity and its combinations on plant biochemistry. Untargeted metabolomics coupled with multivariate statistics pointed out distinct metabolic reprogramming triggered by the different stress conditions, either alone or in combination, differentiating the impact of salinity, drought, and their combination with cold and heat. These results contribute to delving into the impact of various stress combinations, hierarchically highlighting the stress-specific effects and pointing out different interactions.HIGHLIGHTSCombined stresses highlighted synergic and stronger impact on Arabidopsis secondary metabolism, redox imbalance and photosynthetic performance compared to individual stresses. Overall, salinity and its combination were the most impactful.