Energy consumption in new buildings can be reduced at the design stage. This study optimizes the ventilation system design of a new residential building located in a warm climate (Southern Italy). Different system options of horizontal air-ground heat exchangers (HAGHEs), also called earth-to-air heat exchangers (EAHX), have been considered to search for the optimal configuration. The thermal behaviour of the obtained configurations has been modelled by the dynamic simulation software TRNSYS 17. The pipe numbers, the air flow rate, and the soil thermal conductivity are among the simulated building components. For each of them, different design options have been analysed to study how each parameter impacts the building thermal behaviour in winter and summer. The operative air temperature (TOP) has been evaluated inside the building prototype to investigate the indoor comfort. The paper demonstrates that HAGHEs permit to assure a suitable indoor climatization if the building envelope is optimized for a warm area. These conditions require high values of heat storage capacity to keep under control the internal temperature fluctuations, especially in summer. The paper confirms the importance of geothermal systems and design optimization to increase energy savings.