Wheat streak mosaic virus (WMV) from the Potyviridae family is one of the most important viruses infecting wheat in the world and Iran. In this study, metabolic network analysis related to LC-qTOF-MS analysis was investigated in the resistant cultivar Cross Adl 24 hours after inoculation at both optimal (20°C) and high (32°C) temperatures using Metaboanalyst 6.0 software. By measuring the network parameters, it was determined that there were relatively different systemic metabolic responses in the resistant cultivar infected with WSMV at optimal and high temperatures. At optimal temperature, an increase in the expression of nucleotides such as adenine, guanine, and sphingolipids (sphinginine) were observed, which play a role in antiviral defense through the induction of programmed cell death in the accumulation of ROS. On the other hand, a decrease in aromatic amino acids (phenylalanine and tryptophan) was observed, which probably directs carbon sources towards defense pathways. Under high temperature stress, a decrease in number of compounds such as choline (cell membrane destruction at high temperature) and 2-aminobenzoic acid (as virus inhibitor) and an increase in the amino acids proline (increasing plant tolerance to high temperature) and arginine (increasing defense based on RNA silencing and synthesis of proteins related to host stress) occurred. This study showed that resistance to WSMV is the result of precise coordination of multidimensional metabolic networks to combat multiple simultaneous stresses such as pathogens and high temperature. The findings can be used to develop cultivars with sustainable resistance to biotic and abiotic stresses under climate change conditions.