Climate change imposes various extremes, i.e., elevated CO2 and ozone levels, drought, heat waves, erratic and intense rainfall patterns, storms, floods in low-lying lands, and the emergence of pathogens and pests. Higher temperatures and water scarcity result in soil salinity and sodicity. The changing climate, somehow, affects all forms of life, but its impact on crop plants is most obvious, forfeits as crop plants are the main source of food and nutrition. Hence, to respond against the adverse effects of climate change, climate-smart agricultural practices and the development of climate-resilient crops are of pivotal importance for the sustainability of all life forms. Conventional crop breeding has had considerable success, but it is slow and largely limited to exploiting the existing genetic variation in crop plants and their very close relatives. Biotechnology and genetic engineering give us the prospect of creating dramatic alterations in crops to withstand a number of abiotic and biotic stresses, which is difficult to attain using conventional breeding approaches. Modern biotechnological and genetic engineering approaches, such as genome editing, RNA-mediated gene silencing, armored with next-generation sequencing and genome mapping, have paved the way for precise and faster genetic modifications of plants. In the present review, we discussed the impact of climate change on agricultural systems. We summarize the applications and promises of modern biotechnological tools and technologies in generating climate-resilient crops to achieve food and nutrition security in a sustainable manner. We encourage researchers and other stakeholders to engage in activities beyond the laboratory if they hope to see what is technologically possible translated into practice at this critical point in agricultural transformation.