Abstract: Poria cocos is characterized by the dried sclerotium of a fungus in the Polyporaceae family. It can often parasitize on the roots of Pinaceae plants, thereby serving as a commonly used conventional Chinese medicinal material in China. Post-harvest Poria cocos is required for the appropriate primary processing at the origin, before it is used as Chinese herbal decoction pieces. Some primary processing has been widely selected in the main producing areas of Poria cocos, including the static sweating, steam sweating, and pharmacy sweating. Among them, static sweating can share the long processing cycle and high labor intensity. The content of water-soluble polysaccharides can significantly improve their solubility, whereas the content of triterpenoid components can decrease significantly. The steam sweating can be expected for the high processing efficiency and yield. There is a significant decrease in the content of water-soluble polysaccharides. Therefore, the pretreatment can be utilized to retain the medicinal components of Poria cocos. This study aims to clarify the primary processing of Poria cocos at the origin for the high drying efficiency and product quality. The optimal sweating was obtained for the Poria cocos pretreatment. A systematic investigation was made to explore the vacuum-pulsation infrared drying and the quality of Poria cocos cubes. Poria cocos was pretreated by static sweating, steam sweating, and pharmacy sweating. An analysis was carried out on the moisture content and water-soluble polysaccharide content after pretreatment. Furthermore, the Poria cocos was cut into cubes of 8, 12 and 16 mm after sweating treatment under different vacuum times (2, 5, 10, 15 and 25 min) and atmospheric pressure times (2, 4, 8 and 12 min). Finally, the drying performance was evaluated on the crushing rate, shrinkage rate, color, and water-soluble polysaccharide content. The pretreatment results indicated that the moisture content of Poria cocos peels remained unchanged during steam sweating, while the red Poria cocos and Poria cocos varied from 49.87% and 51.95% to 52.57% and 53.84%, respectively. However, the steam sweating led to the inactivation of the mycelium of Poria cocos, thus preventing the secondary growth. In static sweating, there was a decrease in the moisture content of Poria cocos peels, red Poria cocos, and Poria cocos. In pharmacy sweating, there was a gradual decrease in the moisture content of Poria cocos and Poria cocos peels. The moisture content of red Poria cocos at the end of sweating was higher than that of static sweating. Both static sweating and pharmacy sweating were involved in the secondary growth. The water-soluble sugar content was the highest after 3 days of pharmacy sweating, leading to optimal sweating. The vacuum pulsed infrared drying test was performed on the Poria cocos cubes. The results showed that the drying time increased first and then decreased with the increase of vacuum time and normal time. The smaller the size of Poria cocos cubes were, the shorter the drying time was. The smaller the size of Poria cocos cubes, the higher the breakage rate and the lower the shrinkage rate were; The larger the size, the lower the breakage rate was, and the higher the shrinkage rate was. The brightness (L*) decreased first and then increased with the extension of vacuum time and normal time. And the content of water-soluble polysaccharides increased first and then decreased with the extension of vacuum time. When the size of Poria cocos cubes was 12 mm, the vacuum time was 10 min, and the normal time was 4 min, the high drying efficiency and dry product quality were achieved with a breakage rate and shrinkage rate of 22.45% and 25.42%, respectively, L* of 53.25, and a water-soluble polysaccharide content of 35.21 mg/g. The optimal sweating was identified for the Poria cocos pretreatment. The optimal vacuum pulsed infrared drying was determined for high efficiency and quality control during drying. The finding can provide a specific and feasible technical solution to the modern and standardized production of Poria cocos.