Yacon, a perennial plant from the Andean region, is particularly rich in fructo-oligosaccharides (FOS) and inulin. However, these saccharides are rapidly hydrolyzed after harvest, affecting the functional characteristics of yacon. Therefore, a preservation technology such as drying is warranted to preserve the FOS content of yacon products during the off-season. To this end, we dried yacon slices, either untreated or pretreated with pulsed vacuum osmotic dehydration (PVOD), in a microwave vacuum (MWV). PVOD was performed using a sorbitol solution (38 °Brix, 35 °C, and 681 mmHg during the first 10 min). A three-level experimental design with three initial power densities (PDs) of 3.6, 6.3, and 9.9 W.g−1 and three vacuum pressures (VPs) of 0, 300, and 600 mmHg was employed to perform the MWV drying experiments. FOS content, drying kinetics, diffusivity, shrinkage, yacon temperature, and rehydration were investigated. We observed that during PVOD, as microwave PD increased, the drying time, moisture, and water activity decreased. Moreover, an increase in PD positively affected FOS retention, diffusivity, temperature, and shrinkage. Furthermore, VP significantly affected FOS retention in pretreated samples and facilitated drying. In addition, microwaves with a higher PD increased the effective diffusivity and facilitated FOS retention. VP also affected the drying and FOS retention of pretreated samples. In general, yacon browning was observed under all treatment conditions, independent of pretreatment. For osmotically dehydrated samples, processing conditions with a PD of 9.9 W.g−1 and vacuum pressure of 600 mmHg are ideal for drying yacon slices via microwave vacuum, thereby increasing the FOS content by approximately 40%.