Drought, exacerbated by climate change, threatens global food security, particularly impacting crop products, including tomatoes, which are economically essential but drought sensitive. This study explores drought responses in the wild-type Solanum pennellii (WT), known for drought tolerance, and cultivated Solanum lycopersicum (CT), through RNA-Seq analysis at three drought intervals (2 Weeks +5D, +8D, and +11D). Across these points, WT and CT showed 716 and 1459 differentially expressed genes (DEGs), respectively. Pathway enrichment revealed distinct metabolic adaptations: wild varieties prioritized arginine and proline metabolism early, shifting to cutin, suberin, and wax biosynthesis by day 11, while cultivated varieties emphasized steroid biosynthesis, secondary metabolite production, and photosynthesis-related pathways. Transcription factor analysis highlighted HB-HD-ZIP enrichment in wild varieties, contrasting with broader, less coordinated TF activation in cultivated varieties. WGCNA identified the blue module as significantly associated with prolonged drought in both species. Network analysis showed ribosomal pathways enriched in CT, while in WT, it was observed broader pathway enrichment, including secondary metabolites, carbon metabolism, and oxidative stress pathways. In WT unique hub genes were, sucrose synthase and malate synthase, suggesting specialized drought adaptation mechanisms. These findings highlight multifaceted drought resilience strategy of WT compared to growth-focused response of CT, offering a foundation for breeding drought-resistant tomato varieties critical for food security under climate pressures.

At times of rapid global climatic changes, refining drought tolerance in tomatoes is a demanding concern. Drought-resistant wild tomato relatives offer a valued resource for studying drought response mechanisms and leveraging them for breeding. To understand drought-response mechanisms in Solanum, we performed an integrated gene expression, transcription factor (TF), and network-based analysis in wild (Solanum pimpinellifolium L.) and cultivated (Solanum lycopersicum L.) tomato species with differing drought tolerance. This integrated analysis unveiled distinct gene expression patterns under drought stress in both species. Ethylene-responsive factors (ERFs) were notably the most significantly expressed transcription factors in both varieties. Additionally, species-specific TF expression was observed, such as Ethylene Insensitive3-like (EIL) and MIKC_MADS in the wild type, and Zinc Finger homeodomain (ZF-HD) in the cultivated variety. Differential expression pattern in ROS rummaging and heat shock proteins was observed in the top DEGs of both species. Network analysis highlighted shared genes involved in crucial pathways like jasmonic acid biosynthesis, the protein kinase pathway, and reactive oxygen species foraging in both species. Notably, the wild variety showed altered expression of genes associated with jasmonic acid/ethylene biosynthesis, antioxidant response, heat shock proteins, and cell wall remodeling. These observations offer insights into the differences in drought response in both species and suggest the role of jasmonic acid/ethylene biosynthesis, antioxidant response and ROS scavenging as significant factors contributing to improved drought tolerance in S. pimpinellifolium.