Microbial fuel cell (MFC) is lauded for its potentials to solve both energy crisis and environmental pollution. Technologically, it offers the capability to harness electricity from the chemical energy stored in the organic substrate with no intermediate steps, thereby minimizes the entropic loss due to the inter-conversion of energy. The sciences underneath such MFCs include the electron and proton generation from the metabolic decomposition of the substrate by microbes at the anode, followed by the shuttling of these charges to cathode for electricity generation. While its promising prospects were mutually evinced in the past investigations, the upscaling of MFC in sustaining global energy demands and waste treatments is yet to be put into practice. In this context, the current review summarizes the important knowledge and applications of MFCs, concurrently identifies the technological bottlenecks that restricted its vast implementation. In addition, economic analysis was also performed to provide multiangle perspectives to readers. Succinctly, MFCs are mainly hindered by the slow metabolic kinetics, sluggish transfer of charged particles, and low economic competitiveness when compared to conventional technologies. From these hindering factors, insightful strategies for improved practicality of MFCs were formulated, with potential future research direction being identified too. With proper planning, we are delighted to see the industrialization of MFCs in the near future, which would benefit the entire human race with cleaner energy and the environment. Display omitted •The fundamentals and applications of microbial fuel cells were summarized.•The hindering factors for upscaling of microbial fuel cells were discussed.•Economic analysis for microbial fuel cell technologies was performed.•Insightful strategies to improve microbial fuel cells' practicality were proposed.