More than 70% of land's cultivated area is affected by alkaline salinity stress. Our previous research focused on comparative studies of Arabidopsis thaliana demes with differential performance under neutral (neuSAL) and alkaline salinity (alkSAL) due to local adaptation. Here, an integrated analysis on leaf physiological, nutritional, endogenous phytohormonal and transcriptomic traits was performed to understand differences in the molecular response mechanisms to each salinity type. Higher sensitivity to alkSAL was observed in demes adapted to siliceous soils due to a decreased internal Fe use efficiency, and sequence variation detected at β-CA1 and α-CA1 loci is proposed to contribute to such Fe homeostasis imbalance. Moreover, dissection on DEGs shared by neuSAL and alkSAL confirmed enhanced inhibition of central features on primary and secondary metabolism in these demes under alkSAL. The cell wall and vacuolar β-galactosidase BGAL4 was revealed as a candidate for favoring stress-regulated cell wall rearrangement under neuSAL but not under alkSAL, due to pH-restricted enzymatic activity. Weighted correlation network analysis confirmed the involvement of the identified candidates in co-expression modules significantly correlating with favorable responses to neuSAL and alkSAL. Overall, the present study provides useful insights into key targets for breeding improvement in alkaline saline soils.