The building sector accounts for approximately 40% of global final energy consumption, with residential buildings representing a particularly intensive share. In Iran, residential energy demand is nearly double that of comparable countries, despite the introduction of National Building Code Regulation No. 19, which emphasizes the importance of envelope insulation, glazing, and mechanical efficiency. This study addresses a critical omission in both research and regulation: the role of interior design in shaping energy outcomes. By integrating artificial intelligence (AI) methodologies with performance simulation, the research evaluates the impact of interior variables—including surface reflectance, furniture layout, window treatments, lighting systems, and flooring materials—on the energy efficiency of a prototypical 95-m² apartment in Shiraz. A hybrid methodology combines EnergyPlus simulations with a genetic algorithm supported by artificial neural network surrogate models to explore more than 5000 design configurations. The results demonstrate that AI-optimized interiors can reduce annual energy use intensity by 24.6%, decrease cooling demand by 29%, cut lighting energy by 41%, and modestly lower heating demand by 9%, while simultaneously improving spatial daylight autonomy by 63% and reducing predicted dissatisfaction from 15% to 10%. Sensitivity analysis establishes a hierarchy of influence, identifying surface reflectance, efficient lighting, and adaptive shading as the most impactful interventions. Robustness testing confirms the resilience of optimized solutions under variable infiltration and occupancy conditions. The findings reposition interior design as a central determinant of energy efficiency, challenge reductionist definitions that prioritize envelopes and systems alone, and demonstrate AI’s ability to balance competing objectives of efficiency, comfort, and daylight quality. The study concludes that extending Regulation No. 19 to include interior parameters offers a cost-effective and equitable pathway to improve performance across Iranian housing, democratizing efficiency while advancing national sustainability goals.