The key factors that affect HVAC load calculations include building envelope characteristics, such as insulation, windows, and walls; internal heat gains from occupants, lighting, and equipment; and external factors like climate, solar radiation, and wind. Other factors, such as occupancy schedules, equipment efficiencies, and ductwork layout, also play a crucial role in determining the accurate HVAC load. A thorough understanding of these factors is essential to perform accurate load calculations.