An integrated model of a two-step process for the ex situ bioremediation of xenobiotic contaminated soil has been formulated. The process is characterized by an initial extraction step of the organic contaminants from the polluted soil by contact with inexpensive and commercially-available polymer beads, followed by release and biodegradation of the xenobiotics, with parallel polymer bioregeneration, in a Two-Phase Partitioning Bioreactor (TPPB). The regenerated polymer is cyclically reused in the extraction step, so reflecting the robust and otherwise-inert properties of such polymers. The model was calibrated and validated for a soil contaminated with 4-nitrophenol (4NP) and treated with the DuPont polymer Hytrel 8206. In the model calibration, the partition coefficient polymer-soil, Pps, and the mass transfer coefficient, K, were evaluated, as 105.3 and 0.24 h−1 respectively. A diffusion coefficient within the polymer of 6.3 10−8 cm2 s−1 was determined from the fitting of sorption/desorption data. The model was then tested for two alternative process configurations consisting of either one or two soil extraction units, followed by the biodegradation/bioregeneration step. The latter configuration resulted in more effective polymer utilization and is suitable if each extraction step requires a shorter time than the regeneration step. The model predicted that an extraction time of 12 h was sufficient to reach removal efficiencies ≥90% while the biodegradation/bioregeneration step required 24 h to reach efficiencies ≥93%, with a good agreement with experimental data (R2 > 0.98 for both cases). The simulation of the process operated with two extraction units showed a better performance with a final concentration ∼0.2 g4NP kgds−1 vs. 1.69 g4NP kgds−1 obtained with single extraction unit, for a soil contaminated with 10 g4NP kgds−1. Corresponding extraction efficiencies were 96 and 83%, respectively.