In this review, we synthesize evidence for NGF/BDNF signaling as a regulatory pathway in osteosarcoma immunity; delineate mechanistic interactions linking neurotrophin receptors to tumor and immune compartments; define measurable biomarker readouts across tumor tissue and biofluids; and evaluate therapeutically actionable strategies that target this axis, including rational combinations with immunotherapy. The gene discussed is BDNF; the disease is neoplasm.