To fully leverage the advantages of both hot air drying and radio frequency vacuum drying, a segmented combination drying technique was applied to post-harvest Cistanche. This new drying method involves using hot air drying in the initial stage to remove the majority of free water, followed by radio frequency vacuum drying in the later stage to remove the remaining small amount of free water and bound water. During the radio frequency vacuum drying (RFV) phase, the effects of temperature (45, 55, and 65 °C), vacuum pressure (0.020, 0.030, and 0.040 MPa), plate spacing (65, 75, and 85 mm), and slice thickness (4, 5, and 6 mm) on the drying characteristics, quality, and microstructure of Cistanche slices were investigated. Additionally, infrared thermal imaging technology was used to examine the surface temperature distribution of the material during the drying process. The results showed that compared to radio frequency vacuum drying alone, the hot air-radio frequency combined drying significantly shortened the drying time. Under conditions of lower vacuum pressure (0.020 MPa), plate spacing (65 mm), and higher temperature (65 °C), the drying time was reduced and the drying rate increased. Infrared thermal imaging revealed that in the early stages of hot air-radio frequency vacuum combined drying, the center temperature of Cistanche was higher than the edge temperature. As drying progressed, the internal moisture of the material diffused from the inside out, resulting in higher edge temperatures compared to the center and the formation of overheating zones. Compared to natural air drying, the hot air-radio frequency vacuum combined drying effectively preserved the content of active components such as polysaccharides (275.56 mg/g), total phenols (38.62 mg/g), total flavonoids (70.35 mg/g), phenylethanoid glycosides, and iridoids. Scanning electron microscopy observed that this combined drying method reduced surface collapse and cracking of the material. This study provides theoretical references for future drying processes of Cistanche.