Tobacco is smoked by different techniques through cigarette and shisha smoking. The prevalence of tobacco is considered one of the major threats to public health. This study aims to assess the effect of cigarette, shisha, and mixed (cigarette/shisha) smoking on heavy metal contamination in hair samples, hair loss, and DNA fragmentation, to correlate age, incidence of hair loss, and smoking duration with the amount of accumulated metals and the DNA fragmentation, and to correlate the level of heavy metal contamination with DNA fragmentation. This study was implemented in Saudi Arabia among sixty males divided into four groups (15/group): control and cigarette, shisha, and mixed smokers. Heavy metal contamination in hair samples and urinary DNA levels were assayed. All metal and urinary DNA levels were significantly elevated in cigarette, shisha, and mixed smokers compared to non-smokers. Hair loss was also higher among smokers especially among participants with high DNA concentrations. There were positive significant correlations of age and incidence of hair loss with urinary DNA concentration. There were positive significant correlations between urinary DNA concentration and all heavy metal levels. Cigarette, shisha, and mixed smoking trigger metal contamination, DNA fragmentation, and hair loss. Moreover, hair loss was observed to be associated with Sb, Cd, and Ni as well as urinary DNA level, while age was associated only with lead and urinary DNA levels. The duration of smoking had a major impact on Pb and Sb levels. Finally, contamination with all six metals was significantly associated with DNA fragmentation.