Purpose <p>Despite advances in treatment, many nasopharyngeal carcinoma (NPC) survivors face substantial and enduring quality of life (QOL) impairments. This systematic review and meta-analysis aims to explore trends and factors influencing QOL in NPC patients across various treatment modalities over time, to inform patient-centered care strategies.</p> Methods <p>A systematic search of five databases was performed for studies published between January 2000 and August 2024. Eligible studies included adult NPC patients receiving primary treatment, with longitudinal QOL assessments using the EORTC QLQ-C30 and/or QLQ-H&amp;N35. Meta-analyses of mean differences across four timepoints were conducted: baseline, short-term (0–3&#xa0;months after treatment), medium-term (4–6&#xa0;months after treatment), and long-term (7–24&#xa0;months after treatment). Subgroup analysis compared radiotherapy (RT) alone versus RT with chemotherapy (RT + CT). Only changes that were both statistically significant and exceeded established minimally clinically important difference thresholds were considered clinically meaningful.</p> Results <p>A total of 2979 patients from 17 studies were included. Across all treatments, many QOL domains worsened post-treatment, with partial recovery by the medium term. Compared to baseline, global QOL, emotional and social function improved in the long term, while dry mouth and sticky saliva had persistently large deteriorations. RT + CT patients experienced a sharper initial decline but showed greater medium-term recovery in some domains compared to RT-only patients, though this was confounded by disease stage.</p> Conclusion <p>NPC treatment causes significant short-term QOL impairment, with partial recovery. However, persistent long-term issues remain, highlighting the need for long-term supportive care and targeted rehabilitation to improve patient-centered care in NPC.</p>