A healthcare resource allocation generally plays a vital role in the number of patients treated (pnt) and the patient waiting time (wt) in healthcare institutions. This study aimed to estimate pnt and wt as output variables by considering the number of healthcare resources employed and analyze the cost of health resources to the hospital depending on the cost coefficient (δi) in an emergency department (ED). The integration of the discrete-event simulation (DES) model and machine learning (ML) algorithms, namely random forest (RF), gradient boosting (GB), and AdaBoost (AB), was used to calculate the estimation of the output variables depending on the δi of resources cost. The AB algorithm performed best in almost all scenarios based on the results of the analysis. According to the AB algorithm based on the δ0.0, δ0.1, δ0.2, and δ0.3, the accuracy data were calculated as 0.9838, 0.9843, 0.9838, and 0.9846 for pnt; 0.9514, 0.9517, 0.9514, and 0.9514 for wt, respectively in the training stage. The GB algorithm had the best performance value, except for the results of the δ0.2 (AB had a better accuracy at 0.8709 based on the value of δ0.2 for pnt) in the test stage. According to the AB algorithm based on the δ0.0, δ0.1, δ0.2, and δ0.3, the accuracy data were calculated as 0.7956, 0.9298, 0.8288, and 0.7394 for pnt; 0.8820, 0.8821, 0.8819, and 0.8818 for wt in the training phase, respectively. All scenarios created by the δi coefficient should be preferred for ED since the income provided by the pnt value to the hospital was more than the cost of healthcare resources. On the contrary, the wt estimation results of ML algorithms based on the δi coefficient differed. Although wt values in all ML algorithms with δ0.0 and δ0.1 coefficients reduced the cost of the hospital, wt values based on δ0.2 and δ0.3 increased the cost of the hospital.