Indoor microbiomes associated with heating, ventilation, and air-conditioning (HVAC) systems represent distinct built environment niches that influence microbial functional potential relevant to indoor air quality. This study investigated date-specific and spatial variability in predicted antibiotic resistance- and virulence-associated functions within HVAC-associated microbiomes in a mechanically ventilated public-use building. Environmental samples from indoor air, supply air, exhaust air, and HVAC surfaces were analyzed using 16S rRNA gene sequencing combined with predictive metagenomic profiling (PICRUSt2). The predicted functional profiles were dominated by efflux pump systems and metal resistance, suggesting adaptation to chemical- and material-related stressors in HVAC environments. March samples showed higher overall enrichment of predicted resistance-associated functions and stronger genus-level clustering, particularly within Cellulosimicrobium, Pseudomonas, and Paracoccus, whereas June samples exhibited lower predicted resistance potential but higher predicted virulence-associated functions on ventilation surfaces. Predicted functional signals were most frequently associated with supply air and HVAC surfaces, indicating compartment-specific accumulation and transport patterns. The recurrent co-occurrence of predicted resistance- and virulence-associated functions within the same taxa is consistent with multifunctional adaptive potential, although genomic context was not assessed. These findings provide a preliminary basis for microbiological exposure assessment and sustainable indoor air quality management in mechanically ventilated buildings.