Significant research efforts are directed towards finding new ways to reduce the cost, increase efficiency, and decrease the environmental impact of power-generation systems. The poly-generation concept is a promising strategy that enables the development of a sustainable power system. Over the past few years, the Proton Exchange Membrane Fuel Cell-based Poly-Generation Systems (PEMFC-PGSs) have received accelerated developments due to the low-temperature operation, high efficiency, and low environmental impact. This paper provides a comprehensive review of the main PEMFC-PGSs, including Combined Heat and Power (CHP) co-generation systems, Combined Cooling and Power (CCP) co-generation systems, Combined Cooling, Heat, and Power (CCHP) tri-generation systems, and Combined Water and Power (CWP) co-generation systems. First, the main technologies used in PEMFC-PGSs, such as those related to hydrogen production, energy storage, and Waste Heat Recovery (WHR), etc., are detailed. Then, the research progresses on the economic, energy, and environmental performance of the different PEMFC-PGSs are presented. Also, the recent commercialization activities on these systems are highlighted focusing on the leading countries in this field. Furthermore, the remaining economic and technical obstacles of these systems along with the future research directions to mitigate them are discussed. The review reveals the potential of the PEMFC-PGS in securing a sustainable future of the power systems. However, many economic and technical issues, particularly those related to high cost and degradation rate, still need to be addressed before unlocking the full benefits of such systems.