In recent years manifold-microchannel technology has received considerable attention from the research community as it has demonstrated clear advantage over state of the art heat exchangers. It has the potential to improve heat transfer performance by an order of magnitude while reducing pressure drop penalty equally impressive, when compared to state of the art heat exchangers for selected applications. However, design of heat exchangers based on this technology requires selection of several critical geometrical and flow parameters. This research focuses on the numerical modeling and an optimization algorithm to determine such design parameters and optimize the performance of manifold-microchannels for a plate heat exchanger geometry. A hybrid method was developed to calculate the total pumping power and heat transfer of this type of heat exchangers. The results from the hybrid method were successfully verified with the results obtained from a full CFD model and experimental work. Based on the hybrid method, a multi-objective optimization of the heat exchanger was conducted utilizing an approximation-based optimization technique. The optimized manifold-microchannel flat plate heat exchanger showed superior performance over a Chevron plate heat exchanger which is a wildly used option for diverse applications.