With global warming and climate change, abiotic stresses often simultaneously occur. Combined salt and heat stress was a common phenomenon that was severe, particularly in arid/semi-arid lands. We aimed to reveal the systematic responsive mechanisms of tomato genotypes with different salt/heat susceptibilities to combined salt and heat stress. Morphological and physiological responses of salt-tolerant/sensitive and heat-tolerant/sensitive tomatoes at control, heat, salt and combined stress were investigated. Based on leaf F_v/F_m and H₂O₂ content, samples from tolerant genotype at the four treatments for 36 h were taken for transcriptomics and metabolomics. We found that plant height, dry weight and net photosynthetic rate decreased while leaf Na⁺ concentration increased in all four genotypes under salt and combined stress than control. Changes in physiological indicators such as photosynthetic parameters and defence enzyme activities in tomato under combined stress were regulated by the expression of relevant genes and the accumulation of key metabolites. We screened five key pathways in tomato responding to a combination of salt and heat stress, such as oxidative phosphorylation (map00190). Synergistic regulation at morphological, physiological, transcriptional and metabolic levels in tomato plants was induced by combined stress. Heat stress was considered as a dominant stressor for tomato plants under the current combined stress. The oxidative phosphorylation pathway played a key role in tomato in response to combined stress, where tapped key genes (e.g. alternative oxidase, Aox1a) need further functional analysis. Our study will provide a valuable resource important for studying stress combination and improving tomato tolerance.