Aim: Advances in radiotherapy (RT), chemotherapy (ChT), and prolonged survival have increased the incidence of second primary malignancies (SPMs) in patients with nasopharyngeal carcinoma (NPC). This study evaluated NPC survivors’ SPM incidence and characteristics. Methods: Medical records of patients with NPC treated between 1990 and 2019 were retrospectively reviewed. SPMs were classified by organ, histopathology, and location (in-field or out-of-field RT). All SPMs were histopathologically confirmed. Cumulative SPM incidence was estimated, clinical associations were analyzed, and standardized incidence ratios (SIRs) were calculated. Results: Among 821 patients with NPC, 79 (9.6%) developed SPMs over a median follow-up of 90 months (interquartile range [IQR]:34–157). Independent risk factors included age >40 years (hazard ratio [HR]:4.02; 95% confidence interval [CI]:2.20–7.34) and female sex (HR: 1.73; 95% CI: 1.00–2.98). Synchronous SPMs occurred in 14 patients, while metachronous SPMs occurred in 65. Twenty-five (38.4%) of the 65 metachronous SPMs are located within the radiation field. The overall SPM risk was 73% higher than in the general population (SIR:1.73; 95% CI:1.69–1.77). SPMs were most frequently in the head and neck (n=25) and lungs (n=15). Excess cancer risks were significant for head and neck (SIR:34.69; 95% CI:33.49–35.89), sarcoma (SIR:14.18; 95% CI:13.03–15.33), esophagus (SIR:6.18; 95% CI:5.35–7.01), kidney (SIR:4.62; 95% CI:4.22–5.01), and pancreas (SIR:4.12; 95% CI:3.72–4.51). Conclusion: NPC survivors face an elevated risk of SPMs. Long-term follow-up should monitor both in-field and out-field malignancies. Decades-long comprehensive monitoring is recommended, with emphasis on neoplasms outside the irradiation field.