BACKGROUND Tuberculosis is prevalent, especially in low-income countries. The most devastating manifestation of tuberculosis is central nervous system (CNS) involvement, albeit rare. CASE REPORT We report a rare case of a 26-year-old woman with morbid obesity and hepatitis C who had cerebral tuberculoma and was treated with an extended duration of anti-tuberculosis multi-drug therapy. This patient was initially diagnosed with disseminated tuberculosis of the lungs, liver, and peritoneum. After 4 months of anti-tuberculosis treatment, she developed new right temporal hemianopia and new cerebral tuberculoma, which was identified on repeated magnetic resonance imaging (MRI) and was attributed to tuberculosis-immune reconstitution inflammatory syndrome. The anti-tuberculosis treatment was continued; however, she gained large amounts of weight, which resulted in the failure of the anti-tuberculosis treatment of the cerebral tuberculoma. We decided to adjust the anti-tuberculosis drug dosage using her total body weight, and she responded well, with a decrease in size of the cerebral tuberculoma. The anti-tuberculosis treatment was subsequently stopped after 3 years because of clinical and imaging improvement. CONCLUSIONS This case illustrates the challenges faced in the treatment of cerebral tuberculoma, which, in this case, included a high body mass index affecting drug dosage and confounding an inadequate treatment response as seen on interim MRI, resulting in prolonged duration of anti-tuberculosis treatment. Persistent enhancement seen on brain MRI does not equate to treatment failure.