Indoor air temperature (IAT) and indoor relative humidity (IRH) are the prominent microclimatic variables; still, potential contributors that influence the homeostasis of livestock animals reared in closed barns. Further, predicting IAT and IRH encourages farmers to think ahead actively and to prepare the optimum solutions. Therefore, the primary objective of the current literature is to build and investigate extensive performance analysis between popular ML models in practice used for IAT and IRH predictions. Meanwhile, multiple linear regression (MLR), multilayered perceptron (MLP), random forest regression (RFR), decision tree regression (DTR), and support vector regression (SVR) models were utilized for the prediction. This study used accessible factors such as external environmental data to simulate the models. In addition, three different input datasets named S1, S2, and S3 were used to assess the models. From the results, RFR models performed better results in both IAT (R² = 0.9913; RMSE = 0.476; MAE = 0.3535) and IRH (R² = 0.9594; RMSE = 2.429; MAE = 1.47) prediction among other models particularly with S3 input datasets. In addition, it has been proven that selecting the right features from the given input data builds supportive conditions under which the expected results are available. Overall, the current study demonstrates a better model among other models to predict IAT and IRH of a naturally ventilated swine building containing animals with fewer input attributes.