Advanced glazing systems can reduce global building energy consumption and enhance thermal comfort in office environments; however, the integrated performance of next-generation window glazing technologies, characterized by moderate-to-high thermal resistance (R-4 to R-23 ft²·°F·hr/Btu), remains insufficiently understood. This study investigated how next-generation xenon- and vacuum- based IGUs compared to a conventional argon-filled double-pane low-e IGU regarding building energy use, thermal comfort, and economic performance across various window-to-wall ratios (WWRs). Building performance simulations were conducted for a south-facing unshaded modular office in a hot-humid climate (2A ASHRAE climate zone) using a customized parametric workflow developed in Honeybee (Grasshopper) through EnergyPlus. Four state-of-the-art IGU configurations were evaluated across WWRs of 30-60% under controlled HVAC and building envelope conditions by assessing (1) annual heating and cooling loads, (2) energy use intensity (EUI), (3) predicted mean vote (PMV), (4) predicted percentage of dissatisfied (PPD), and (5) cost-effectiveness. The results demonstrate that the investigated next-generation IGUs consistently outperformed the baseline argon-based model in terms of energy efficiency and thermal comfort across all WWRs. The triple xenon low-e IGU 02 delivered the highest overall performance, reducing EUI by 13–22% and annual cooling loads by 21-30% while maintaining an annual average PPD below 5.6%. It also substantially reduced thermal discomfort, decreasing occupied hours with PPD >10% from 176-662 hours for the baseline to 0-36 hours. The double-pane vacuum and hybrid triple-pane vacuum systems (IGU 03 and IGU 04) also delivered notable energy and comfort improvements over the baseline. From an economic perspective, however, IGU 03 proved the most cost-effective solution, achieving the shortest payback period of approximately 2.3 years. Overall, the findings demonstrate the potential of the evaluated xenon- and vacuum-based IGU configurations to enhance façade performance and provide architects and engineers with guidance for selecting high-performance glazing systems across diverse façade designs in hot-humid climates.