Recent evidence links high temperatures to increased ozone-related cardiovascular mortality in a changing climate, but the underlying biological mechanisms remain unclear. We investigated the associations between short-term ozone exposure and pro-thrombosis, a key process in the pathophysiology of cardiovascular diseases across varying temperatures (5-30 °C) in a longitudinal panel study of 135 participants in Beijing, China. Pro-thrombotic biomarkers and whole blood transcriptome data were measured repeatedly. Bayesian kernel machine regression revealed that higher serum thromboxane (Tx)B₂ levels were associated with increasing levels of joint exposure to air pollutants over 1 week when ozone rather than other pollutants contributed most to the overall effect. Causal mediation analyses found 715 transcripts associated with an increase in TxB₂ following ozone exposure, which were enriched in pathways, including ribosome, thermogenesis, oxidative phosphorylation, and pathways of neurodegeneration. As the temperature increased, we observed a stronger association between ozone exposure and TxB₂ increase. The TxB₂ increments per interquartile range increase in the one-week average of ozone were 6.6, 13.2, 14.8, 16.6, and 18.4 units when the temperatures were 6.5, 15.0, 17.6, 21.4, and 26.7 °C, respectively. The number of mediating transcripts enriched in pathways related to translation, environmental adaptation, energy metabolism, and human diseases was also greater at higher temperatures than at lower ones. This study suggests that higher temperatures exacerbate ozone-related pro-thrombotic response, providing a biological basis for the increased risk of ozone-associated cardiovascular mortality at high temperatures.