The effect of using reduced pressure and absence of oxygen during the spray drying process for processing sensitive compound was investigated. Orange essential oil emulsion was atomized in the same equipment (nozzle and drying chamber) and dried under two different conditions: (a) conventional spray drying settings (airflow at ambient pressure with inlet/outlet temperatures of 190 °C/90 °C); (b) reduced-pressure conditions (10–15 kPa) for allowing water evaporation at 25–30 °C. Emulsion phase was preliminarily characterized regarding droplet size distribution, kinetic stability, microstructure, and rheological behavior in order to ensure that the formulation is able to stabilize the oil droplets. The particles recovered in both process conditions were characterized with respect to the moisture content, water activity, particle size distribution, powder morphology, encapsulation efficiency, wettability, and solubility. The particles produced by vacuum spray drying presented lower mean diameter (14.38 μm) and wettability (94 s) besides higher encapsulation efficiency (99.89%) and moisture content (6.27%) than particles resulting from the conventional process. The vacuum process employed did not affect the solubility of the samples. For both processes, most of the particles presented no apparent fissures or cracks in the structure, but some morphological changes were caused by the vacuum. The process seems to be a promising technique to produce thermo-sensitive powder and can improve technological properties.