Maize (Zea mays L.) is one of the most important strategic crops in Egypt and globally, yet its cultivation in newly reclaimed land in Egypt faces challenges due to saline groundwater. Therefore, developing new maize genotypes with true resilience to salt stress is a sustainable strategy for addressing the gap in maize production. In this work, we investigate the physiological and molecular responses of two Egyptian maize hybrids (SC 168 and SC 176) with contrasting reactions to long-term saline agriculture. SC 168 (salt tolerant) exhibited less severe wilting and discoloration in shoot tissues compared to SC 176, which completely perished. The accumulated Na+ in shoots significantly increased in SC 176 compared to SC 168 under salt stress, with a 3.5-fold increase. In the same context, SC 168 accumulated 1.8 times more K+ than SC 176 under salt stress. Lipid peroxidation of the cell membrane was much more pronounced in the salt-sensitive genotype SC 176 than in SC 168, with a 1.7-fold increase. At the level of gene expression profile, several salt-stress marker genes were examined. The salt-tolerant maize hybrid SC 168 accumulates more mRNA of ZmNHX5 (sodium sequestration in vacuoles), the catalase gene (antioxidative enzyme), and ZmNR (nitrogen assimilation) under salt stress compared to SC 176. Collectively, it is concluded that minimizing sodium ions uptake, enhancing antioxidative power, and maintaining nutritional balance are the main maize salt-resilience strategies that should be considered in developing maize genotypes suitable for saline agriculture.