The pace at which the climate is changing, the food and nutritional security of the projected 9.6 billion world population is at stake due to an increase in the frequency and intensity of climate extremes. Unless crops tolerant to abiotic stresses are developed, the productivity of many crops is likely to be reduced up to 50%. Though genetic augmentation remains a viable option, spectacular progress in developing truly abiotic stress-tolerant crop varieties has not yet developed exploiting the available resources. Therefore, stable signature molecules and genes encoding such molecules will be required for transfer to an agricultural background to develop climate-smart crops. Such clues can be obtained from the “Treasure Trove” present in the metagenomes of extreme environments which have witnessed each ladder of millions of years of evolution and remain undisturbed. Understanding and mining relevant genes/alleles of interest will be pivotal in our quest to develop climate-smart varieties through advanced tools of genetic engineering to ensure food and nutritional security to the ever-growing world population. This book chapter is designed to provide input in that direction.