This paper investigates and analyzes a typical multi-zone office building’s annual energy performance for the location and climate data of central Belgrade. The aim is to evaluate the HVAC system’s and HR unit’s performance in order to conduct the most preferable heating and cooling solution for the typical climate of Belgrade city. The energy performance of four HVAC system types (heat pump - air to air, gas-electricity, electrical and fan coil system) was analyzed, compared and evaluated on a virtual office building model in order to assess the total annual energy performance and to determine the efficiency of the HR unit’s application. Further, the parameters of an energy efficient building envelope, HVAC system, internal loads, building operation schedules and occupancy intervals were implemented into the multi-zone analysis model. The investigation was conducted in EnergyPlus simulation engine using system thermodynamic algorithms and surface/air heat balance modules. The comparison and evaluation of the obtained results was achieved through the conversion of the calculated total energy demand into primary energy. The goal is conduct the most preferable heating and cooling solution (Best Case Scenario) for the climate of Belgrade city and outline major criteria in qualitative enhancement.