This paper presents details of an experimental investigation into the effect of different spacings (ΔX = 2.5 mm, 5.0 mm, 7.5 mm and 10.0 mm) in plate heat exchanger (PHE) on the basis of its combined energetic and exergetic performance by using various nanofluids, i.e., TiO2, Al2O3, ZnO, CeO2, hybrid (Cu+Al2O3), graphene nanoplate (GNP) and multi-walled carbon nanotube (MWCNT). On the basis of experiment data, various energetic and exergetic performance parameters have been evaluated and their inter-relationship has been discussed. The optimum heat transfer characteristics in the nanofluids and their exergetic performance have been found to be achieved with a spacing of ΔX = 5.0 mm. Based on these data, it has been found that the MWCNT/water nanofluid, with a spacing of ΔX = 5 mm in PHE, has the maximum heat transfer coefficient, which is 53% higher compared to water at 0.75 vol % (optimum). Nanofluids significantly improve heat transfer capacity with a nominal rise in pressure drop at 0.75 vol %. This study will help to understand the process of heat transfer augmentation by using various nanofluids in the PHE on the basis of energetic and exergetic performance of the system.