This study investigated regional variations in hospitalization expenses for lung malignant tumor patients within tertiary hospitals. Using H City as the reference point and comparing it with B, M, and C cities, we analyzed factors influencing these expenses. Utilizing data from primary lung cancer inpatients treated throughout 2023 at eight representative tertiary hospitals across the four cities, path analysis was employed to systematically assess the effects of key determinants on hospitalization costs. The findings aim to identify actionable strategies for alleviating patient financial burdens and optimizing the allocation of medical resources. The results of multiple linear regression analysis and path analysis of hospitalized patients with lung malignant tumors in different regions showed that hospitalization days and surgical status were the main factors affecting the total cost of hospitalization, suggesting that optimizing hospitalization procedures and standardizing surgical indications may be an important focus of cost control. The standardized regression coefficients are high in all cities, indicating that these two factors have a consistent and significant economic impact. The effects of gender, age, comorbidities and healthcare financing type are different in different cities. The model with hospitalization duration as the dependent variable further confirmed that surgical intervention, age, and comorbidity presence influenced length of hospital stay and indirectly affected total hospitalization costs. Regional structural and institutional disparities in lung malignant tumor treatment expenses were observed, with cost drivers exhibiting complex interdependencies. These findings indicate a need for further standardization of medical insurance payment systems and clinical practices. Implementation of enhanced cost structure monitoring is recommended to guide evidence-based optimization of clinical pathways, with targeted interventions on cost-sensitive categories such as Western medication and miscellaneous expenses. Concurrently, region-specific cost containment strategies should be developed to improve healthcare resource allocation efficiency and promote equitable, sustainable development of medical services.