Genetically enhancing drought tolerance and nutrient use efficacy enables sustainable and stable wheat production in drought-prone areas exposed to water shortages and low soil fertility, due to global warming and declining natural resources. In this study, wheat plants, exhibiting improved drought tolerance and N-use efficacy, were developed by introducing GmTDN1, a gene encoding a DREB-like transcription factor, into two modern winter wheat varieties, cv Shi 4185 and Jimai 22. Overexpressing GmTDN1 in wheat resulted in significantly improved drought and low-N tolerance under drought and N-deficient conditions in the greenhouse. Field trials conducted at three different locations over a period of 2-3 consecutive years showed that both Shi 4185 and Jimai 22 GmTDN1 transgenic lines were agronomically superior to wild-type plants, and produced significantly higher yields under both drought and N-deficient conditions. No yield penalties were observed in these transgenic lines under normal well irrigation conditions. Overexpressing GmTDN1 enhanced photosynthetic and osmotic adjustment capacity, antioxidant metabolism, and root mass of wheat plants, compared to those of wild-type plants, by orchestrating the expression of a set of drought stress-related genes as well as the nitrate transporter, NRT2.5. Furthermore, transgenic wheat with overexpressed NRT2.5 can improve drought tolerance and nitrogen (N) absorption, suggesting that improving N absorption in GmTDN1 transgenic wheat may contribute to drought tolerance. These findings may lead to the development of new methodologies with the capacity to simultaneously improve drought tolerance and N-use efficacy in cereal crops to ensure sustainable agriculture and global food security.