<p>This study investigated the content of trace elements in the fingernails of Vietnamese men with laryngeal cancer and healthy individuals. Fingernail samples from 54 patients and 50 healthy individuals were analyzed using total reflection X-ray fluorescence (TXRF). To ensure accurate multielement analysis, samples were digested using an HNO₃–HCl mixture before TXRF measurement. Of the eighteen elements identified, the contents of Cr, Ni, Cu, Zn, As, Cd, and Pb were significantly higher in patients than in controls (<i>p</i> &lt; 0.05). Higher contents of these elements were also found in patients with smoking habits. Moreover, patients residing in industrial and agricultural areas were found to have significantly high levels of Cr, Ni, As, Cd, and Pb. Spearman’s analysis revealed significant positive correlations between Ni, Cd, and Pb contents and smoking status; meanwhile, As and Pb showed strong correlations with the patient’s place of residence. Element-element interaction analysis revealed strong internal correlations among the trace elements, particularly between toxic pairs such as Cr–Cu, Ni–Cd, and As–Pb. The Principal Component Analysis (PCA) results validate and elaborate on the preliminary findings obtained from the Spearman correlation analysis. These findings suggest that fingernail elemental analysis is a reliable, non-invasive tool for assessing chronic exposure to toxic metals and identifying high-risk populations. Targeted environmental health interventions, tighter pollution controls, and biomonitoring strategies are urgently needed to reduce heavy metal exposure and contribute to disease prevention, including laryngeal cancer, in Vietnam.</p>