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This article discusses the case of a patient with melanoma-associated leptomeningeal disease (LMD) who was successfully treated with concurrent intrathecal (IT) nivolumab and targeted therapy (TT). LMD is a challenging condition associated with poor prognosis, and treatment options have been limited. However, recent data suggests that IT injection of anti-PD1 antibodies, such as nivolumab, may be a promising approach. In this case, the patient showed a clinical and radiological response to the treatment, with relief of neurological symptoms and no disease progression. This approach may offer a potential alternative for patients with LMD. [Extracted from the article]