The presence of Xenobiotic Organic Compounds (XOCs) in municipal wastewater treatment plants’ effluent raises a global concern due to the easy consumption of these micropollutants by organisms. The fate of XOCs removal mechanisms of these compounds remains a challenge in recent scientific research. This study aimed to create an uncalibrated mathematical fate model within the professional wastewater modeling simulation software in a first step that was able to address the fate of Sulfamethoxazole (SMX), its metabolite, and Nonylphenol ethoxylates (NPEOs) along with conventional compounds during an activated sludge process. For the calibration process as a next step, two different case studies were created with assigning related removal mechanisms to each group of compounds. In the calibration process, model parameters are tuned such that the model can best simulate the experimental data using optimization methods. The validation results showed that the proposed model successfully simulates the removal of XOCs. Results of sensitivity analysis showed that the fate model is more sensitive to biodegradation rate constant than Solid Retention Time (SRT).