With buildings representing a substantial portion of global energy consumption, exploring alternatives to traditional fossil fuel-based heating and cooling systems is critical. Thermoelectricity offers a promising solution by converting temperature differentials into electrical voltage or vice versa, enabling efficient indoor thermal regulation. This paper presents a comprehensive investigation into the integration of thermoelectric wall systems for sustainable building climate control through numerical simulations and experimental analyses. Numerical simulations using computational fluid dynamics (CFD) techniques were conducted to model fluid flow and heat transfer within the thermoelectric wall systems under various operating conditions. These simulations provided insights into the system’s thermal behavior, which were validated through experimental setups designed to measure temperature differentials, airflow rates, and power consumption. The results showed that power consumption is directly correlated with electrical current, ranging from 0.19 W to 77.4 W as the current increased from 0.1 A to 2 A. Additionally, the heat absorbed by the system increased significantly with electrical current, by 706–1044%, depending on the air velocity. The thermal energy released from the hot side of the thermoelectric modules also rose substantially, ranging from 9850 to 5285% with increasing electrical current, and from 275 to 51% with higher air velocities. Moreover, increasing air velocity led to a 6.78–9.37% reduction in power consumption for currents between 0.1 A and 2 A. The coefficient of performance (COP) analysis revealed that optimizing both electrical current and air velocity is essential for maximizing system efficiency. While fan power consumption reduces COP at higher air velocities, neglecting fan power consumption results in COP improvements ranging from 6.5 × 10⁻⁴ to 49.0%. These findings highlight the potential of thermoelectric wall systems to enhance indoor comfort and energy efficiency in buildings.