Wheat streak mosaic virus (WSMV) causes an economically important disease in wheat and other gramineous plants in the world and Iran. Considering global climate change, the incidence of combined drought and heat stresses will considerably influence plant-pathogen interactions and likely increase the virus incidence in the future. So far, little information has been obtained about abiotic stress-virus interactions in plants. To evaluate wheat resistance to WSMV at low temperature and resistance breakdown at high temperature, we analyzed metabolic and volatile organic compounds (VOC) profiles of resistant (Adl-cross) and susceptible (Marvdasht) wheat cultivars to WSMV. Metabolites detected by LC-QTOF/MS in leaves of R and S plants at 24,48 and 72 hours post infection (hpi). WSMV and mock inoculated plants were used for discriminating the most significant metabolites and the metabolic pathways affected at both temperatures. At 24 hpi and 48 hpi at 20°C, the most important metabolites in R plants were coumarins, limited number of lipids, and unknown compounds, while in 72 hpi, in addition to coumarins, alkaloids and several amino acids were increased. Compared to 24 and 48 hpi, at 72 hpi, in R plants most metabolic pathways were up-regulated at 20°C. The resistances related specific pathways were amino acid metabolism, lipid metabolism and alkaloids pathways. The combined heat stress and pathogen related pathways were lipid metabolism and amino acid metabolism pathways. Some carbohydrate metabolism pathways were considered as heat stress related pathways and could be associated to resistance breakdown. On the other hand, the increased expression of lipid compounds especially at 24 hpi at 32°C in R plants can be attributed to plant adaptation to combined stressors such as pathogen and high temperature. Increased susceptibility of R plants at 32°C was coincided with a down-regulated expression of components of signal transduction pathways or in a decreased level of metabolites related to this pathway especially at a later time after infection leading to decreased metabolite signaling. Reduction of signaling components under combined stresses, is possibly brought by deactivating WSMV specific signaling networks leading to susceptibility response in R plants. In addition, VOCs were detected in leaves of R and S plants infected to WSMV at 20°C and 32°C at 24, 48 and 72 hpi by GC.MS-HS-SPME. At 20°C the compounds such as 6-methyl-5-hepten-2-one, heptanal, Z-1,5-octadien-3-ol showed the highest abundance in R plants compared to S plants at an earlier time especially, 48 hpi. Also, at 32°C, VOCs including heptanal, undecanal, farnesyl acetate and 2-pentenal had the most increased amounts at a later time. On the other hand, in R plants, several pathways were up-regulated commonly at 20°C and 32°C. Although, these pathways, were activated more rapidly at 20°C. At 32°C, most of these pathways were up-regulated at 72 hpi. The most important pathways related to combined stresses were included Lipoxygenase, cuticular wax biosynthesis, fatty acid and lipid biosynthesis. Phenyl ethanol biosynthesis pathway was up-regulated only at 32°C, which is probably related to tolerance to heat stress. In this study, we analyzed the transcriptome of R plants infected by WSMV by RNA-Seq at 72 hpi at 32°C. In total, 53,178 genes were affected in this interaction, of which 954 genes showed differential expression significantly at the 0.01 level. Several transcripts included pathogenesis-related protein genes, RNA-silencing genes, heat shock protein genes, transcription factor genes, protein kinase genes and auxin and lipoxygenase pathways genes were up-regulated, while most genes related to cell wall biosynthesis and chlorophyll biosynthesis showed down regulation. In addition, several pathways were significantly induced in wheat, including phenylpropanoid biosynthesis, secondary metabolite biosynthesis and metabolic pathways. These findings revealed that the recent increase of global temperature and the challenge of the breakdown of temperature-sensitive resistance should be considered more than ever. Key Words: Metabolome analysis, WSMV, VOCs, RNA-Seq, Triticum aestivum , temperature-sensitive resistance