Over 67 % of the energy demand within the pharmaceutical and semiconductor industries is for their cleanrooms, driven by stringent temperature and humidity control requirements. Despite high energy usage, heating, ventilation, and air-conditioning (HVAC) units consisting of conventional vapor compression systems (CVCS) are favoured for their simplicity. Hybrid cooling systems (HCS) offer potential efficiency gains by separating latent and sensible loads. Still, reliance on fossil-fuel-fired or electric heaters to regenerate the desiccant makes it energy intensive and reduces CO2 mitigation benefits. This study explores high-temperature heat pumps to simultaneously cool process air and heat regeneration air, thereby using multiple benefits. Heat pumps with condensing temperatures of 80 °C, 90 °C, and 120 °C and an ejector-enhanced trans-critical CO2 heat pump were compared with CVCS and HCS. The 120-bu and CO2HP configurations demonstrated a system COP of 2.94 and 3.22, respectively, surpassing CVCS, which has a system COP of 1.44. These setups achieved CO2 emission reduction of 51 % and 55.2 %, compared to CVCS, respectively.