Concrete is a heterogeneous material that is extensively used as a construction material. However, to improve the toughness and mechanical properties of concrete, various ingredients (fillers) have been added in the past. The addition of nanomaterials for the improvement of the aforementioned properties has attracted many researchers worldwide. The high surface area, high reactivity, and finer size of various nanomaterials have made them preferable for the enhancement of durability, as well as compressive and flexural strength. The aim of the current research is focused on the estimation of compressive strength for the concrete modified with various nanomaterials using two machine learning techniques, namely decision tree technique (DTT) and random forest technique (RFT), and comparison with existing models. The database is collected for different percentages of four major widely used nanomaterials in concrete, i.e., carbon nanotubes, nano silica, nano clay, and nano alumina. The other four input variables used for the calibration of the models are: cement content (CC); water–cement ratio (W/C); fine aggregate, i.e., sand (FA); and coarse aggregate (CA). Both DTT and RFT models were developed for 94 collected experimental datasets from the published literature. The predicted results are further validated through K-fold cross-validation using correlation coefficient (R2), mean absolute error (MAE), root mean square error (RMSE), relative root mean square error, relative square error (RRMSE), and performance index factor (PiF). The RFT model was found to have the lowermost MAE 3.253, RMSE 4.387, RRMSE 0.0803, and performance index factor (PiF) 0.0061. In comparison, predicted results overall revealed better performance and accuracy for the RFT-developed models than for DTT and gene expression programming (GEP) models, as illustrated by their high R2 value, equal to 0.96, while the R2 value for DTT and GEP was found 0.94 and 0.86, respectively.