BACKGROUND Multidrug-resistant tuberculosis (MDR-TB) continues to pose a serious public health challenge, especially when associated with tuberculous meningitis (TBM), which complicates treatment due to the need for central nervous system (CNS) penetration and non-oral administration routes. This case report describes a 24-year-old woman with MDR pulmonary tuberculosis and tuberculous meningitis (TBM) successfully treated with a combination of pyrazinamide, levofloxacin, cycloserine, and linezolid. CASE REPORT A previously healthy 24-year-old woman from Jilin Province, China presented with fever, headache, and impaired consciousness. Chest computed tomography (CT) showed centrilobular nodules and tree-in-bud appearances, while magnetic resonance imaging (MRI) revealed basal meningeal enhancement and tuberculomas. Acid-fast bacilli (AFB) were detected on smear microscopy of cerebrospinal fluid (CSF), and culture confirmed Mycobacterium tuberculosis. Drug susceptibility testing confirmed MDR-TB. Due to impaired consciousness, the treatment regimen was selected based on CNS penetration and enteral administration compatibility. A combination of pyrazinamide, levofloxacin, cycloserine, and linezolid was administered over 18 months. Bedaquiline and pretomanid were not used due to insufficient CNS penetration data at the time and limited availability in Japan. The patient required prolonged mechanical ventilation and was discharged in a minimally conscious state after 541 days. CONCLUSIONS This case highlights the importance of individualized drug selection for MDR-TB with CNS involvement. In managing tuberculosis, especially in low-incidence countries, the epidemiological background of the patient's country of origin should also be considered. Early diagnosis and appropriate drug selection were critical to the patient's survival despite severe neurological sequelae.