In the era of global warming, stress combinations instead of individual stresses are realistic threats faced by plants, which affect the metabolic activities in an inimitable mode unlike individual stress. In the current study, charcoal rot disease stress caused by notorious fungal pathogen viz., Macrophomina phaseolina (Tassi) Goid coupled with toxic levels of heavy metal copper (Cu) was investigated on morpho-physio-biochemical and molecular responses in mash bean [Vigna mungo (L.) Hepper] plants. Soil application with 2% Farmyard manure (FYM) was also used as a warfare agent against the stress/s responses in the plans. Therefore, soil spiked Cu (50 and 100 mg/kg) was inoculated with the pathogen, amended with 2% FYM was sown with mash bean seeds. The individual stress of MP or Cu resulted in more drastic changes in biological (growth, biomass, and yield), and physio-biochemical [(total chlorophyll content, carotenoids, reducing sugar total protein content, and total phenolic, catalase (CAT), peroxidase (POX) and polyphenol oxidase (PPO)] attributes with the greater translocation factors and bioaccumulation factors as compared to stress combination. The expression levels of catalase, ascorbate peroxidase, cytokinin-resistant gene as well as protein profiling and other metabolic changes (activity of CAT, POX, and PPO) were more up regulated under single stress conditions by mash bean plants. Alteration in studied parameters in mash bean plants provided the basis of cross-tolerance (hormesis) induced by Cu against the pathogen under stress combination. Nonetheless, 2% FYM in soil encounters the negative effect of stress responses provoked by the pathogen, Cu or both by decreasing Cu uptake by the plants. FYM worked better at lower concentrations (50 mg/kg) of Cu than at higher ones (100 mg/kg), hence could be used as a suitable option to reclaim soil health and better plant productivity.