This study reveals the economic burden and regional differences of hospitalized Tuberculosis patients in Guangdong Province. Diagnostic costs and western drug costs are the main factors contributing to changes in hospitalization costs, with hospital class, drug resistance and surgery being the main influences, while hospitalization costs will decline over the next three years. Therefore, investing in primary care to improve local healthcare access, empowering providers to manage tuberculosis effectively, optimizing treatment policies, expanding health insurance coverage, and enhancing drug-resistant patient treatment are critical to reducing financial burdens and improving tuberculosis control.