Bone marrow involvement (BMI) of solid tumors is a special type of distant metastasis. It has an occult onset, atypical clinical and laboratory features, and a high mortality. We present a nasopharyngeal carcinoma case with cervical and axillary lymph nodes, bilateral lung, multiple bone, and bone marrow metastases, who was treated chemotherapy plus targeted therapy under the guidance of a patient-derived tumor xenograft (PDTX) model, followed by maintenance chemotherapy plus immunotherapy. The patient's symptoms were relieved after four cycles of chemotherapy plus targeted therapy. His bone marrow biopsy turned negative after 7 months of therapy. In addition, his total peripheral T cells as well as the proportion of CD8+ T cells increased during the course of therapy. The combination of chemotherapy, targeted therapy, and immunotherapy provides an effective antitumor regimen for advanced NPC patients with BMI.