The main purpose of this study was to investigate the influence of ethylcellulose (EC) coating and curing conditions on the quality attributes of pharmaceutical pellets prepared using a quality by design (QbD) approach. The drug release rate of methimazole, a freely soluble model drug, was evaluated extensively together with the mechanical strength and true density of the coated pellets. Moreover, the thermal and spectroscopic properties, as well as the surface characteristics were studied using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Drug layering and EC coating of the pellets were performed in a fluid bed granulator. The results of thermal and infrared analyses showed the absence of significant interactions between the drug and the EC. The regression model was developed to predict the dependent variables (drug release at time 1 h, 4 h, 8 h, and 12 h, hardness of coated pellet, and true density). The results showed that the degree of coating and curing had the most significant effects on all response variables. The design space was built in accordance with the drug release rate following failure probability analysis using Monte Carlo simulations. Robustness and accuracy were also successfully validated and the control variables were optimized. The results highlighted the importance of the optimization in process parameters using the QbD strategy to achieve consistent quality of the pharmaceutical coating process.