Organic carbon and nitrogen content in low-strength wastewaters can be removed by conventional aerobic processes such as Modified Ludzak Ettinger (MLE), but these treatment methods are not appropriate for treating strong wastewaters. Treatment of highly polluted effluents from slaughterhouse, food processing, brewery, dairy, landfill leachates, etc., which are rich in organic matter and nutrients requires specific considerations. The main removal pathways in the aerobic processes are bacterial assimilation and complete nitrification-denitrification for nitrogen content removal which is accompanied by organic carbon removal during this process. Various biological aerobic treatment processes and operations have been tried in the past to effectively treat strong streams, but high energy requirement and sludge production are serious drawbacks. Anaerobic digestion (AD) is the best alternative to the aerobic processes for treatment of strong wastewaters but biological nutrient removal is not possible, and needs further treatment. In high-strength wastewater treatment, neither aerobic nor anaerobic treatment methods alone as a single-process can produce treated effluents complying with discharge standards. Therefore, existing conventional technologies for treatment of highly polluted streams are combined systems. These conventional combined systems are a pair of at least two separate processes in series. Most of the combined systems are applying the AD as a head system which is followed by a polishing aerobic process such as conventional activated sludge. Synchronizing two different processes in a series in combined systems is expensive and complicated with intensive operation and maintenance requirements. Hence, in order to prevail these difficulties, it is paramount to develop an efficient and less expensive single-process technology with simple operation and maintenance. In this thesis, a conventional MLE system as a single-process was modified for treating highly polluted wastewaters, with a performance similar to the combined systems. This modified system is referred to throughout the thesis as SAO/PND (Simultaneous Anaerobic Oxidation/Partial Nitrification–Denitrification). After several unsuccessful modifications were tried, the main successful modifications were increasing the hydraulic retention time (HRT) in the pre-anoxic reactor, and decreasing the solids retention time (SRT) to create favorable conditions for anaerobic oxidation and partial nitrification-denitrification. A laboratory-scale of SAO/PND was used to conduct the experiments in this research. SAO/PND looks like the MLE process regarding the reactor configurations and recycle and return lines. Ammonia concentrations above 150 mg/L can be toxic for the MLE system, but SAO/PND improves the situation so that ammonia concentration is not toxic until close to 290 mg/L. Another issue with MLE process is that it requires high amounts of oxygen and alkalinity which results in high amounts of sludge production. But, SAO/PND produces less sludge, and does not need high amounts of oxygen and alkalinity. The results showed more than 95% chemical oxygen demand (COD) and 90% total inorganic nitrogen (TIN) removal from synthetic wastewater, respectively, in our laboratory environment. In addition, volumetric design loading rates determined as 11.80 kg COD/(m3.d) and 0.63 kg TIN/(m3.d) with synthetic solution as a feed. Furthermore, the results showed high performance of the system in treating dairy and brewery industry effluents. In this modified single-process system, organic carbon was removed through anaerobic oxidation, assimilation, P–uptake by polyphosphate accumulating organisms (PAOs) and denitrifying PAOs (DPAOs), aerobic heterotrophs, and denitrification by DPAOs and denitrifying ordinary heterotrophic organisms (OHOs). Nitrogen content removal mechanisms were assimilation, partial nitrification–denitrification, anaerobic ammonium oxidation (anammox), and small portion uncharacterized processes. 95% and 90% less oxygen requirements along with 60% and 44% less sludge production compared to the conventional aerobic processes and conventional combined systems, respectively, resulted in significant potential cost savings by this modified system. Finally, the applied modified single-process system in this thesis is found as a sustainable, robust, cost-effective, and small footprint process with less intensive operation and maintenance requirements which will yield new insights into the design of treating highly polluted streams in the future.