For a significant period, conventional breeding and genetic modification were the key techniques that were effective in managing biotic and abiotic stresses in crops and adding desirable traits. However, the recent appearance of novel diseases and unexpected climatic changes that have substantial implications for agriculture worldwide have urged scientists to look for alternative methods to quickly manage seasonal crises. The primary emphasis of this chapter is on the obstacles and diverse biotechnological methods employed to enhance crop resilience against a range of biotic and abiotic stressors in plants. Furthermore, we consider gene transformation, omics techniques, genome editing, and other sophisticated biotechnological tools that utilize transcriptomic, proteomic, metabolomic, phenomics, RNA interference, and epigenome modifications for enhancing plant resilience. Lastly, we examine the potential of merging these eco-friendly and innovative methods with conventional breeding to promote modern agriculture and aid in enhancing tolerance to different biotic, abiotic stresses and growth promotion.