<p>Indoor Environmental Quality (IEQ) in office settings plays a critical role in occupant satisfaction and well-being, directly influencing health, productivity, and overall quality of life. Current research, however, lacks an integrated understanding of the mechanisms linking sensory IEQ comfort to satisfaction and well-being. Furthermore, many studies overlook the interactive effects of IEQ across different functional spaces, which may lead to biased estimations of IEQ’s impact on well-being. To address these gaps, this study collected 264 valid questionnaires from employees across nine floors in four office buildings. The survey encompassed sensory IEQ Comfort, Total Environmental Comfort Vote (TECV), Work Environmental Satisfaction (WESA), Work Satisfaction (WSA), and Life Satisfaction (LSA). A multi-group Structural Equation Model (SEM) was employed for multi-spatial integrated analysis. The results indicate that Sensory IEQ comfort in Leisure Space (LS) exhibits more significant pathways to LSA compared to Work Space (WS). In both WS and LS, IEQ comfort promotes WESA and WSA primarily through the mediation of TECV; notably, the impact of WESA is more pronounced in LS. WSA serves as a stronger driver of LSA than WESA in the office. The multi-spatial model significantly reduced the effect sizes of independent pathways compared to single-space models, suggesting that neglecting spatial diversity may lead to result errors. Furthermore, computer usage time was identified as a core factor influencing WESA and WSA, and indirectly affecting LSA. This study provides explicit design guidance for optimizing sensory IEQ to enhance occupant well-being and emphasizes the necessity of multi-spatial considerations in office design.</p>