The standard first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC) is currently a combination of a programmed cell death protein-1 (PD-1) blockade and gemcitabine-cisplatin. However, effective options beyond second-line settings are limited, and a recommended regimen is currently unavailable. This report presents a case study highlighting the significant efficacy of onatasertib, a dual mechanistic target of rapamycin (mTOR) 1/2 inhibitor, in overcoming resistance to immunotherapy in patients with R/M-NPC. A 28-year-old female patient who was diagnosed with nasopharyngeal carcinoma (NPC) experienced tumor relapse following progression on multiple lines of therapy, including immunotherapy. Subsequently, the patient participated in a phase I/II study (TORCH-2) investigating the combination of onatasertib and toripalimab in patients with advanced solid tumors. The patient achieved a nearly complete remission (CR) and experienced a progression-free survival (PFS) of 16 months. This unique case report highlights the efficacy of onatasertib, a dual mTOR1/2 inhibitor, in treating patients with R/M-NPC who have developed resistance to immunotherapy. The occurrence of a grade 2 serious adverse event (AE) underscores the importance of monitoring patients closely during treatment and the need to adjust dosages when necessary to minimize AEs. Meanwhile, it is important to note that the small sample size in this case is a significant limitation. Therefore, further randomized clinical trials are required to evaluate the efficacy and safety of this combination treatment in patients with acquired immunotherapy resistance and R/M-NPC.