With growing concerns on global warming, exergy-based design methods for energy hubs (EHs) in the urban context have been recently investigated to promote more rational and efficient use of energy sources. This study aims to compare exergy-based multi-objective optimization for energy hubs with two primary energy-based methods. The comparison has been performed for Italy and Switzerland, two countries with diverse markets and national electricity production mixes, to indicate the generalizability of our findings. An apartment building in Vevey, Switzerland, was selected to provide domestic hot water demand and structural data to the space heating demand dynamic simulation, for which different TRY weather data have been used for the two countries. Once a superstructure for the energy supply system had been defined, a MILP framework was developed, minimizing a weighted sum of exergy and cost. Using different weights for the two objectives, a Pareto frontier was obtained for each scenario, defining the best possible trade-off solutions between economic and exergetic objectives. The same optimization methodology was performed using total or non-renewable primary energy as an objective. The use of a boiler and PV panels is preferred when primary energy-based methods are applied, while the use of heat pumps and solar thermal panels is preferred when exergy-based method is applied. As a result, the exergy-based method seems to be the most effective as the carbon intensity of the electricity decreases, providing solutions with lower CO2 emissions and reasonable costs in the future when national electricity production will be gradually decarbonized. In addition, a sensitivity analysis of the exergy method was carried out to analyze the influence of key parameters such as energy prices and energy demand variation on the optimized energy system. In addition, the renovation scenarios of the case study building were presented, revealing different optimal setups of the energy hub as the weight of investment costs increases.