Methyl Perfluoroisobutyl Ether (HFE7100) is a new type of spray coolant, which has high volatility, low boiling point, low toxicity, and high latent heat of evaporation. As an evaporative coolant for aerospace and electronic equipment, HFE7100 has good application prospects, and its evaporation mechanism has attracted considerable attention. To this end, we investigate the evaporation process of HFE7100 droplets on the brass and glass sub-strates by using the droplet shape analysis system and analyze the effect of temperature and thermal conductivity of substrate on the evaporation of HFE7100 droplet. The results show that, when the substrate temperature is the same, the droplet evaporation time on the brass substrate with high thermal conductivity is less than that on the glass substrate with low thermal conductivity. With the increase of substrate temperature, the decrease of evaporation time on brass substrate with high thermal conductivity is greater (23.8%, 62.5%). Meanwhile, the contact angle and the contact radius of HFE7100 droplets on the two substrates decrease obviously during the evaporation process, but the decreasing trend was different. When the substrate temperature is lower than the ambient temperature, with the passage of evaporation time, the contact angle and the contact radius of the HFE7100 droplets evaporating on the two substrates shows a tendency of first rapid decline, then slow decline, and finally rapid decline. When the substrate temperature is higher than the ambient temperature, the contact angle and the contact radius of HFE7100 droplet evaporating on the glass substrate with low thermal conduc-tivity still maintains the above trend, while the contact angle of HFE7100 droplet evaporating on the brass substrate with high thermal conductivity decreases rapidly until the end of evaporation. In addition, the evap-oration mode of HFE7100 droplets is mixed mode, which is different from that of conventional droplets such as water. With the increase of the substrate temperature, the bulge height of the droplets on the brass substrate with high thermal conductivity increases, while this phenomenon is not obvious on the glass substrate with low thermal conductivity. This work offers further knowledge of sessile HFE7100 droplet evaporation, which, in turn, provide a reference for the process optimization of its applications in spray coolant for electronics.