The extensive use of inhalational anesthetics contributes to both indoor and outdoor (environmental) pollution. The influence of genetic susceptibility on DNA damage and oxidative stress and the possible modulation of gene expression have not yet been investigated upon occupational exposure to waste anesthetic gases (WAGs). This study assessed 8-oxoguanine DNA glycosylase 1 (OGG1) and superoxide dismutase 2 (SOD2) gene expression, which are related to oxidized DNA repair and antioxidant capacity, respectively, and the influence of their polymorphisms (OGG1 rs1052133 and SOD2 rs4880) in 100 professionals highly exposed to WAGs and 93 unexposed volunteers (control group). Additionally, X-ray repair cross complementing 1 (XRCC1 rs25487 and rs1799782) and ataxia telangiectasia mutated (ATM rs600931) gene polymorphisms as well as genetic instability (micronucleus-MN and nuclear bud-NBUD) and oxidative stress (malondialdehyde-MDA and ferric reducing antioxidant power-FRAP) biomarkers were assessed in the groups (control and exposed) and in the subgroups of the exposed group according to job occupation (anesthesiologists versus surgeons/technicians). Except for the ATM TT controls (associated with increased FRAP), there were no influences of OGG1, XRCC1, ATM, and SOD2 polymorphisms on MN, NBUD, MDA, and FRAP values in exposed or control subjects. No significant difference in the expression of either gene evaluated (OGG1 and SOD2) was found between the exposed and control groups. Increased OGG1 expression was observed among OGG1 -/Cys individuals only in the control group. Among the exposed group, anesthesiologists had a greater duration of WAG exposure (both h/week and years) than surgeons/technicians, which was associated with increased MDA and decreased antioxidant capacity (FRAP) and SOD2 expression (redox status). Higher expression of OGG1 was found in -/Cys surgeons/technicians than in anesthesiologists with the same genotype. Increased antioxidant capacity was noted in the surgeons/technicians carrying the ATM T allele and in those carrying XRCC1 -/Gln. Increased MN was influenced by OGG1 -/Cys in surgeons/technicians. Anesthesiologists with ATM CC exhibited increased MN, and those carrying the C allele (CC/CT genotype) exhibited increased NBUD. SOD2 polymorphism did not seem to be relevant for WAG exposure. These findings contribute to advancing the knowledge on genetic susceptibility/gene expression/genetic instability/oxidative stress, including differences in job occupation considering the workload, in response to occupational exposure to WAGs.