BACKGROUND Conventional wastewater treatment plants (WWTPs) cannot degrade completely emerging pollutants such as pharmaceuticals and pesticides. The release of such contaminants through WWTP effluents or sludge disposal is of high environmental concern. Hydrothermal treatment has been adopted as alternative treatment technology for sludge to recover energy and valuable products. This study demonstrates the removal of inherent concentration levels of organic pollutants from the previous classes under variable reaction conditions, i.e. temperature, reaction time and sludge‐to‐water (%wt) ratio. RESULTS Response surface methodology (RSM) was applied to model removal efficiency for the sum of detected pharmaceutical compounds and to evaluate the significant operational parameters. The results showed that higher values of temperature and time enhanced the percent degradation efficiency while sludge‐to‐water (%wt) ratio was not a significant factor affecting the removal process. The maximum removal efficiency of pharmaceutical residues reached 89.8% under the following conditions: 220 °C, 360 min reaction time, 7.50%wt sludge‐to‐water ratio. Additionally, hydrothermal treatment removed completely trace levels of detected pesticides, regardless of the applied conditions. RSM was also applied separately to those pharmaceuticals (i.e., amisulpride and amitriptyline) detected most frequently and at higher concentrations in sludge samples. Both compounds have been degraded at >90% using reaction temperatures from 205 to 220 °C and reaction time between 297 and 360 min with 7.5% sludge/H2O ratio. CONCLUSION Hydrothermal treatment is a suitable and promising technology for sewage sludge treatment for the efficient destruction of organic pollutants and the production of renewable hydrochars. © 2022 Society of Chemical Industry (SCI).