This study conducts a comprehensive Whole Building Life Cycle Assessment (WBLCA) of a 3,450 m2 commercialresidential mixed-use building located across four climatically distinct cities in Iran: Tehran (semi-arid), Rasht (humid), Yazd (hot-dry), and Mashhad (cold-dry). Three commonly used HVAC configurations-(i) air-cooled chiller with natural gas furnace, (ii) 2-pipe fan coil units, and (iii) DX split heat pumps-are evaluated across twelve climate-system scenarios. A Building Information Modeling (BIM) platform integrated with Carrier HAP 4.9 and SimaPro 9.0 (ReCiPe 2016 H, Ecoinvent v3) was employed to simulate building energy loads and quantify cradle-to-grave environmental impacts. Results indicate that DX split systems reduce total life-cycle carbon emissions by up to 40% compared to centralized systems, particularly in hot and humid zones. Embodied carbon analysis revealed concrete as the most dominant contributor, accounting for 68% of upstream emissions. Substitution with low-carbon Leca-based concrete selected from the Ecoinvent library led to a 12% reduction in embodied impacts. Sensitivity analysis showed that a one-unit increase in HVAC COP can cut operational emissions by approximately 28%. Uncertainty was evaluated using a Monte-Carlo simulation (n = 1,000), confirming robustness within a +/- 9% margin. A blind-run validation approach, calibrated using hourly simulation data and benchmarking against the technical dossier of a comparable case, demonstrated acceptable predictive accuracy (MBE = 4.2%, CVRMSE = 1.03%). The study's novelty lies in its climate-responsive scenario matrix, integration of real equipment data, and its end-to-end automated workflow from BIM modeling to impact assessment. The findings highlight the importance of climate-adaptive HVAC design, use of localized low-impact materials, and digital modelling integration to support national decarbonization goals. Recommendations for future work include incorporating economic and social dimensions into LCA, exploring hybrid HVAC technologies, and applying digital twins for real-time performance feedback.