Changing environmental conditions are limiting crop productivity and, hence, there is an urgent need to develop stress tolerant plants. Engineering of Cis-regulatory elements (CREs) is an effective strategy to design such plants. Transcription factors (TFs) can be used effectively to manipulate gene expression. However, overlapping expression has been observed for several stress-responsive TFs. In order to design improved plants by Cis-engineering, we first need to understand the complex regulatory network of TFs and the cross-talk between them. Advances in systems biology have enabled us to visualize plants from a holistic view during the abiotic stress. The current review discusses major transcriptional regulatory networks involved in abiotic stress tolerance, and how a better understanding of these networks may help in designing stress-tolerant plants. Finally, the review mentions some potential approaches to generate stress-tolerant crops to enhance crop productivity, which is the ultimate goal of all plant genetic engineering studies.