Modeling and prediction of polar organic chemical integrative sampler (POCIS) sampling rates (Rs) for 73 compounds using artificial neural networks (ANNs) is presented for the first time. Two models were constructed: the first was developed ab initio using a genetic algorithm (GSD-model) to shortlist 24 descriptors covering constitutional, topological, geometrical and physicochemical properties and the second model was adapted for Rs prediction from a previous chromatographic retention model (RTD-model). Mechanistic evaluation of descriptors showed that models did not require comprehensive a priori information to predict Rs. Average predicted errors for the verification and blind test sets were 0.03 ± 0.02 L d–1 (RTD-model) and 0.03 ± 0.03 L d–1 (GSD-model) relative to experimentally determined Rs. Prediction variability in replicated models was the same or less than for measured Rs. Networks were externally validated using a measured Rs data set of six benzodiazepines. The RTD-model performed best in comparison to the GSD-model for these compounds (average absolute errors of 0.0145 ± 0.008 L d–1 and 0.0437 ± 0.02 L d–1, respectively). Improvements to generalizability of modeling approaches will be reliant on the need for standardized guidelines for Rs measurement. The use of in silico tools for Rs determination represents a more economical approach than laboratory calibrations.