Heavy metal contamination from occupational sources is a cause for concern due to its potential accumulation in the environment and the body of living organisms, which leads to long-term toxic effects. There is limited evidence on the concentration of heavy metals in the body fluids of welding workers. This study aimed to measure the concentration of nickel (Ni) and chromium (Cr) as two main toxic heavy metals in the urine samples of welders and determine the potential relationship of various environmental factors on their concentration levels. This study was conducted in Iran in 2022–2023. Eighty-five urine samples were collected from the studied welding workers. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to measure the concentration of Ni and Cr. Data related to socio-demographic characteristics (education level, income, work experience, age, and body mass index (BMI)), lifestyle profile (consumption of seafood and canned food, smoking, physical activity), type of ventilation and preventive devices at work, and suffering from underlying diseases (cardiovascular and high blood pressure) were collected using valid questionnaires. Ni and Cr were present in 100% of urine samples with mean concentrations of (1.09 ± 0.294) and (11.45 ± 16.751) µg/g creatinine, respectively. A significant correlation was observed between the mean concentration of Ni and Cr with the level of education, income, work experience, age, consumption of seafood and canned food, smoking, type of ventilation and preventive devices, and underlying diseases (p-value < 0.05). Also, there was no significant difference between Ni concentration and physical activity and Cr concentration with BMI. Lifestyle determinants and not using preventive devices are important predictors of urinary heavy metals in welding workers. Therefore, more research is required to determine the adverse effects of long-term exposure to these heavy metals.