It is difficult to manually process and analyze large amounts of data. Therefore, to solve a given problem, it is easier to reach the solution by studying the data obtained from the environment of the problem with computational intelligence methods. In this study, pool boiling heat flux was estimated in the isolated bubble regime using two optimization methods (genetic and artificial bee colony algorithm) and three machine learning algorithms (decision tree, artificial neural network, and support vector machine). Six boiling mechanisms containing eighteen different parameters in the genetic and the artificial bee colony (ABC) algorithms were used to calculate overall heat flux of the isolated bubble regime. Support vector machine regression (SVMReg), alternating model tree (ADTree), and multilayer perceptron (MLP) regression only used the heat transfer equation input parameters without heat transfer equations for prediction of pool boiling heat transfer over a horizontal tube. The performance of computational intelligence methods were determined according to the results of error analysis. Mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE) error were used to calculate the validity of the predictive model in genetic algorithm, ABC algorithm, SVMReg, MLP regression, and alternating model tree. According to the MAPE error analysis, the accuracy values of MLP regression (0.23) and alternating model tree (0.22) methods were the same. The SVMReg method used for pool boiling heat flux estimation performed better than the other methods, with 0.17 validation error rate of MAPE.