Background Floods cause not only damage but also public health issues. Developing an application to simulate public health problems during floods around the Loei River by implementing geographic information system (GIS) and structural equation model (SEM) techniques could help improve preparedness and aid plans in response to such problems in general and at the subdistrict level. As a result, the effects of public health problems would be physically and mentally less severe. Methods This research and development study examines cross-sectional survey data. Data on demographics, flood severity, preparedness, help, and public health problems during floods were collected using a five-part questionnaire. Calculated from the population proportion living within 300 m of the Loei River, the sample size was 560 people. The participants in each subdistrict were recruited proportionally in line with the course of the Loei River. Compared to the empirical data, the data analysis examined the causal model of public health problems during floods, flood severity, preparedness, and help. The standardized factor loadings obtained from the SEM analysis were substituted as the loadings in the equations for simulating public health problems during floods. Results The results revealed that the causal model of public health problems during floods, flood severity, preparation, and help agreed with the empirical data. Flood severity, preparedness, and aid (χ2 = 479.757, df = 160, p value <.05, CFI = 0.985, RMSEA = 0.060, χ2/df = 2.998) could explain 7.7% of public health problems. The computed values were applied in a GIS environment to simulate public health problem situations at the province, district, and subdistrict levels. Conclusions Flood severity and public health problems during floods were positively correlated; in contrast, preparedness and help showed an inverse relationship with public health problems. A total of 7.7% of the variance in public health problems during floods could be predicted. The analysed data were assigned in the GIS environment in the developed application to simulate public health problem situations during floods.