Microbial desalination cells (MDCs), a recent technological discovery, allow for simultaneous wastewater treatment and desalination of saline water with concurrent electricity production. The premise for MDC performance is based on the principles that bioelectrochemical (BES) systems convert wastewaters into treated effluents accompanied by electricity production and the ionic species migration (i.e. protons) within the system facilitates desalination. One major drawback with microbial desalination cells (MDCs) technology is its unsustainable cathode chamber where expensive catalysts and toxic chemicals are employed for electricity generation. Introducing biological cathodes may enhance the system performance in an environmentally-sustainable manner. This study describes the use of autothrophic microorganism such as algae and Anammox bacteria as sustainable biocatalyst/biocathode in MDCs. Three different process configurations of photosynthetic MDCs (using Chlorella vulgaris) were evaluated for their performance and energy generation potentials. Static (fed-batch, SPMDC), continuous flow (CFPMDC) and a photobioreactor MDC (PBMDC, resembling lagoon type PMDCs) were developed to study the impact of process design on wastewater treatment, electricity generation, nutrient removal, and biomass production and the results indicate that PMDCs can be configured with the aim of maximizing the energy recovery through either biomass production or bioelectricity production. In addition, the microbial community analysis of seven different samples from different parts of the anode chamber, disclosed considerable spatial diversity in microbial communities which is a critical factor in sustaining the operation of MDCs. This study provides the first proof of concept that anammox mechanism can be beneficial in enhancing the sustainability of microbial desalination cells to provide simultaneous removal of ammonium from wastewater and contribute in energy generation.