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Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory demyelinating disease mediated by aquaporin-4 antibodies (AQP4-IgG) and frequently requires long-term immunosuppressive therapy to prevent irreversible neurological and visual disability. Coexistence with systemic lupus erythematosus (SLE) further complicates management. We report a young woman with AQP4-IgG-positive NMOSD who experienced recurrent optic neuritis and myelitis over several years before diagnostic confirmation. Attempts at multiple conventional steroid-sparing immunosuppressive agents were unsuccessful due to reproducible hypersensitivity reactions, later attributed to underlying cutaneous lupus SLE, resulting in prolonged corticosteroid dependence. Although rituximab was initially tolerated and achieved disease stability, relapse occurred when access to therapy was limited by socioeconomic factors. This case highlights the challenges of delivering standard-of-care treatment for NMOSD in real-world settings, where patient-specific factors and treatment accessibility may constrain optimal management, underscoring the need for individualised strategies to prevent cumulative visual and neurological morbidity.