Background: The growing vehicle repair industry with spray facilities has become a key source of volatile organic compounds (VOC) pollution. Predictors of VOC chronic toxic effects on health should be determined. Evaluation of genetic damage in vehicle painters exposed to VOC has a significant role in anticipating health hazards. Aim of the work: Assessment of the potential genotoxicity and its correlation to some predictors and exposure biomarkers among vehicle painters. Subjects and Methods: A cross-sectional study compared 40 exposed vehicle painters to 40 unexposed control participants. Biomarkers of DNA damage (Comet assay), direct DNA oxidative stress markers (8-oxoguanine (8-OxoG) plus 8-hydroxy-2-deoxyguanosine (8-OHdG)), oxidative stress indicators (malondialdehyde (MDA) and glutathione peroxidase (GPx)), then VOC urinary metabolites were investigated. Results: The exposed workers showed significantly higher levels of 8-OxoG, 8-OHdG, and MDA besides declined GPx. Comet assay parameters were significantly higher among the exposed workers, as evidenced by increased tail length, DNA percent in the tail, and tail moment relative to non-exposed. Urinary concentrations of VOC metabolites were considerably higher in the exposed workers relative to non-exposed. Conclusion: According to the exposure-effect correlation analysis, predictors of VOC-induced genotoxicity included the non-use of personal protective equipment, longer duration of exposure, higher concentrations of VOC metabolites, and elevated levels of oxidative damage indicators. Comet assay parameters were significantly correlated with these biomarkers, supporting their role as indicators of DNA damage and the genotoxic risk among vehicle painters. Recommendations: Protective measures besides routine biomonitoring for all workers chronically exposed to VOC.