We used modeling to predict the energy and cost savings associated with the air-based, hybrid membrane-biofilm reactor (hybrid MfBR). This process is obtained by replacing fine-bubble diffusers in conventional activated sludge with air-supplying, hollow-fiber membrane modules. Evaluated processes included removal of chemical oxygen demand (COD), combined COD and total nitrogen (TN) removal, and hybrid growth (biofilm and suspended). Target concentrations of COD and TN were based on high-stringency water reuse scenarios. Results showed reductions in power requirements as high as 86%. The decrease mainly resulted from the dramatically lower air flows for the MBfR, resulting from its higher oxygen-transfer efficiencies. When the MBfR was used for COD and TN removal, savings up to US$200/1,000 m3 of treated water were predicted. Cost savings were highly sensitive to the costs of the membrane modules and electrical power. The costs were also very sensitive to membrane oxidation flux for ammonia, and the membrane life. These results suggest the hybrid MBfR may provide significant savings in energy and costs. Further research on the identified key parameters can help confirm these modeling predictions and facilitate scale-up.