Heavy metals are considered a major occupational hazards in foundry industry, and exposure may result in cytotoxic, genotoxic and DNA damage effects. This study aims to assess blood metal levels namely (Pb, Cd, Cr, Mn, and Ni) and to elucidate their association with blood selenium levels. Moreover, to evaluate cytogenetic alterations and DNA damage along with hematological parameters in foundry workers. This case–control study included 26 male workers (exposure group) and 15 male controls. The biological exposure to cocktail of metals was determined via measuring the blood levels of lead (B-Pb), cadmium (B-Cd), chromium (B-Cr), manganese (B-Mn) and nickel (B-Ni), as well as selenium (B-Se) by inductively coupled plasma optical emission spectrometry (ICP-OES). Additionally, composite exposure index was calculated. Chromosome aberration (CA) and DNA fragmentation were exploited to detect genotoxicity. Hematological parameters were determined on an automated hematology analyzer. Blood metals analysis unveiled significantly elevated levels of B-Pb and B-Cd (P = 0.006; 0.012 respectively), while B-Se level was significantly lower in exposed workers as compared to controls (P = 0.017).The frequency of DNA fragmentation was found to be significantly higher in the exposed group (P = 0.018). Whereas, no statistically significant difference was found between the two groups in regards to CAs, however, the higher frequency of CAs among exposed workers than in controls (23.08%) was found. The level of hemoglobin markedly decreased in workers as compared to controls (P = 0.012). The multiple regression analysis showed that the composite exposure index highly affect the frequency of DNA fragmentation patterns, while B-Pb was the only variable affect the level of B-Se with coefficient of determination (R2 = 0.524; 0.426, P = 0.0001; 0.0001 respectively) among the exposed workers. Taken together, we revealed that the co-exposure to lead and cadmium induced DNA fragmentation and increased chromosomal aberrations in foundry workers.