Evaluating an illness’s economic impact is critical for developing and executing appropriate policies. South Korea has mandatory national health insurance in the form of NHIS that provides propitious conditions for assessing the national financial burden of illnesses. The purpose of our study is to provide a comprehensive assessment of the economic impact of PM2.5 exposure in the subway and a comparative analysis of cause-specific mortality outcomes based on the prevalent health-risk assessment of the health effect endpoints (chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD)). We used the National Health Insurance database to calculate the healthcare services provided to health-effect endpoints, with at least one primary diagnosis in 2019. Direct costs associated with health aid or medicine, treatment, and indirect costs (calculated based on the productivity loss in health effect endpoint patients, transportation, and caregivers, including morbidity and mortality costs) were both considered. The total cost for the exposed population for these endpoints was estimated to be USD 437 million per year. Medical costs were the largest component (22.08%), followed by loss of productivity and premature death (15.93%) and other costs such as transport and caregiver costs (11.46%). The total incurred costs (per 1000 persons) were accounted to be USD 0.1771 million, USD 0.42 million, and USD 0.8678 million for COPD, Asthma, and IHD, respectively. Given that the economic burden will rise as the prevalence of these diseases rises, it is vital to adopt effective preventative and management methods strategies aimed at the appropriate population.