Amidst escalating global population and the tumultuous impacts of climate change, the imperative for robust, high-yielding crops resilient to myriad stresses is more pressing than ever. Soil salinity stands as a formidable barrier to rice production worldwide, curtailing both growth and yield. Consequently, a comprehensive study of response of rice to soil salinity at physiological and molecular strata is indispensable for effective management. Our endeavor encompasses a multifaceted exploration aimed at unraveling and enhancing plant stress responses, particularly towards salinity and drought, in the naturally salt-tolerant coastal wild rice from India. Employing proteomics, metabolomics, transcriptomics, and genomics, we've uncovered a plethora of novel stress-associated proteins (HSPs & SAPs) and metabolic pathways in rice. Notably, our scrutiny of two-component system members, including hybrid-type histidine kinases, through functional genomics tools, has yielded promising insights. Furthermore, delving into candidate genes within the SALTOL QTL has unveiled intriguing facets of their contributions to stress tolerance. A valuable repository of rice mutants (cv IR64), generated via gamma-irradiation, augments our arsenal, facilitating a systems biology approach to elucidate pivotal pathways governing salt and drought tolerance. In the crucible of our research, we forge pathways to safeguard rice yields against the environmental stresses, heralding a future of agricultural resilience and sustenance.