As our planet faces increasing environmental challenges, such as biotic pressures, abiotic stressors, and climate change, it is crucial to understand the complex mechanisms that underlie stress responses in crop plants. Over past few years, the integration of techniques of proteomics, transcriptomics, and genomics like LC-MS, IT-MS, MALDI-MS, DIGE, ESTs, SAGE, WGS, GWAS, GBS, 2D-PAGE, CRISPR-Cas, cDNA-AFLP, HLS, HRPF, MPSS, CAGE, MAS, IEF, MudPIT, SRM/MRM, SWATH-MS, ESI have significantly enhanced our ability to comprehend the molecular pathways and regulatory networks, involved in balancing the ecosystem/ecology stress adaptation. This review offers thorough synopsis of the current research on utilizing these multi-omics methods (including metabolomics, ionomics) for battling abiotic (salinity, temperature (chilling/freezing/cold/heat), flood (hypoxia), drought, heavy metals/loids), biotic (pathogens like fungi, bacteria, virus, pests, and insects (aphids, caterpillars, moths, mites, nematodes) and climate change stress (ozone, ultraviolet radiation, green house gases, carbon dioxide). These strategies can expedite crop improvement, and act as powerful tools with high throughput and instant database generation rates. They also provide a platform for interpreting intricate, systematic signalling pathways and knowing how different environmental stimuli cause phenotypic responses at cellular and molecular level by changing the expression of stress-responsive genes like RAB18, KIN1, RD29B, OsCIPK03, OsSTL, SIAGL, bZIP, SnRK, ABF. This review discusses various case studies that exemplify the successful implementation of these omics tools to enhance stress tolerance in plants. Finally, it highlights challenges and future prospects of utilizing these approaches in combating stress, emphasizing the need for interdisciplinary collaborations and bio-technological advancements for sustainable agriculture and food security.