Microbial fuel cell (MFC) is a novel technology that can be used for electricity generation during oxidization of the organic substances presented in the substrate. To obtain a desirable performance, it is essential to understand the influential factors on the MFC. Among the numerous factors affecting the MFC performance, substrate, microorganisms and their metabolism, electron transfer mechanism in an anodic chamber, electrodes material and the shape of electrodes, type of membrane, operating conditions such as temperature, pH and salinity, electron acceptor in a cathodic chamber and geometric design of the MFC are considered as the most important factors. Among different substrates, wastewater is a sustainable rich medium which can be treated by MFCs. There are various types of exoelectrogenic bacteria presented in wastewaters which can oxidize organic matter and transfer electrons to the anode without using mediators. Like other microbial systems, optimum pH and temperature enhance the bacterial growth which can improve the MFC performance. Despite the negative effect of salt on microbial growth, higher salinity and ionic strength can increase the conductivity of substrate and therefore enhance MFC performance. Scaling up MFC is a controversial issue which needs a comprehensive understanding of these factors. By using new inexpensive materials for electrodes and membrane for manufacturing MFCs, a more cost-effective design for scalable wastewater treatment and high power generation can be achieved. Furthermore, MFC is a suitable candidate for bioremediation of contaminated groundwater. These factors and their impact on the MFC performance have been reviewed in the present survey.