Even though microalgal biomass is leading the third generation biofuel research, significant effort is required to establish an economically viable commercial-scale microalgal biofuel production system. Whilst a significant amount of work has been reported on large-scale cultivation of microalgae using photo-bioreactors and pond systems, research focus on establishing high performance downstream dewatering operations for large-scale processing under optimal economy is limited. The enormous amount of energy and associated cost required for dewatering large-volume microalgal cultures has been the primary hindrance to the development of the needed biomass quantity for industrial-scale microalgal biofuels production. The extremely dilute nature of large-volume microalgal suspension and the small size of microalgae cells in suspension create a significant processing cost during dewatering and this has raised major concerns towards the economic success of commercial-scale microalgal biofuel production as an alternative to conventional petroleum fuels. This article reports an effective framework to assess the performance of different dewatering technologies as the basis to establish an effective two-stage dewatering system. Bioflocculation coupled with tangential flow filtration (TFF) emerged a promising technique with total energy input of 0.041 kWh, 0.05 kg CO2 emissions and a cost of $ 0.0043 for producing 1 kg of microalgae biomass. A streamlined process for operational analysis of two-stage microalgae dewatering technique, encompassing energy input, carbon dioxide emission, and process cost, is presented.