Plants are subjected to various environmental stresses that influence their growth, metabolism, productivity and survival. Nevertheless, plants respond to these stresses by inducing certain morpho-physiological, biochemical, molecular and genetic changes. Some of these changes conferring stress tolerance include the formation of cork/abscission layers and tyloses, gum deposition, synthesis of pathogenesis-related proteins, increased cell lignification and synthesis of signaling molecules. Phytomelatonin is a signaling molecule uniformly distributed in diverse plant parts and regulates physio-biochemical responses under abiotic and biotic stresses. It confers stress tolerance to plants by delaying leaf senescence, reducing photosynthetic inhibition, acting as a biostimulator and improving the antioxidant status. Studies have shown the positive effects of exogenously applied phytomelatonin for stress mitigation that leads to improved seed germination, plant growth, yield and chlorophyll content. Recent research has shown the hidden potential of phytomelatonin in plant tissue culture, wherein it can be used for the production of various stress enzymes and other organic compounds like silymarin. Herein, the review highlights the potential of phytomelatonin in plants along with its underlying mechanism of action to alleviate stress in plants. Also numerous crosstalks of phytomelatonin with other signaling molecules have been highlighted, including nitric oxide, reactive nitrogen species, calcium calmodulin and phytohormones to alleviate stress. It also provides detailed insight into the genetic regulation of stress tolerance in plants, along with brushing the-omics approach of phytomelatonin synthesis and functioning. The present review paves the path for detailed research on the development of transgenic and in-vitro aspect of phytomelatonin in the plant tissue culture. • The present review highlights the overall role of melatonin in plant growth and development and the potential of melatonin in stress alleviation in plants. • The cross-talks of melatonin with other signaling molecules is presented including the role of nitric oxide, calcium calmodulin and phytohormones in stress tolerance. • The-omics approach of melatonin synthesis and functioning is explained. • Role of melatonin in in-vitro aspect of plant tissue culture and applied research by genetic manipulation of melatonin for stress tolerance has been discussed.