Abstract: The effects of different formulations and manufacturing process conditions on the physical properties of a solid dosage form are of importance to the pharmaceutical industry. It is vital to have in-depth understanding of the material properties and governing parameters of its processes in response to different formulations. Understanding the mentioned aspects will allow tighter control of the process, leading to implementation of quality-by-design (QbD) practices. Computational intelligence (CI) offers an opportunity to create empirical models that can be used to describe the system and predict future outcomes in silico. CI models can help explore the behavior of input parameters, unlocking deeper understanding of the system. This research endeavor presents CI models to predict the porosity of tablets created by roll-compacted binary mixtures, which were milled and compacted under systematically varying conditions. CI models were created using tree-based methods, artificial neural networks (ANNs), and symbolic regression trained on an experimental data set and screened using root-mean-square error (RMSE) scores. The experimental data were composed of proportion of microcrystalline cellulose (MCC) (in percentage), granule size fraction (in micrometers), and die compaction force (in kilonewtons) as inputs and porosity as an output. The resulting models show impressive generalization ability, with ANNs (normalized root-mean-square error [NRMSE] =1%) and symbolic regression (NRMSE =4%) as the best-performing methods, also exhibiting reliable predictive behavior when presented with a challenging external validation data set (best achieved symbolic regression: NRMSE =3%). Symbolic regression demonstrates the transition from the black box modeling paradigm to more transparent predictive models. Predictive performance and feature selection behavior of CI models hints at the most important variables within this factor space.