MicroRNAs (miRNAs) are a distinct class of non-coding, small regulatory RNAs which have evolved significantly in generating abiotic stress tolerance across a variety of model plants and crop species. These miRNAs, while undergoing post-transcriptional modifications, have often been found to be linked with epigenetic regulations of stress-responsive gene expression. The discovery of isomers of miRNAs (isomiRs) is also a remarkable event, as some schools of scientists believe them to be regulatory molecules distinct from the conventional miRNAs. The link between isomiRs and abiotic stress responses in plants is now a field of intense research. In this review, we have highlighted the mechanism of various tools and techniques which are essential to visualize high-throughput data analysis. Such data are required for generating large-scale libraries of small RNAs, from which stress-responsive miRNAs are conventionally screened. The concluding part of the review especially contains an exhaustive discussion on the recent developments of miRNA-mediated tolerance towards multiple stresses, such as nutrient deficiency, salinity, drought, oxidative stress, hypoxia, temperature stress, radiation, and heavy metal toxicity. Both transgenic as well as miRNAome approaches have been focussed in this section of the review.