V/Sc multilayer has been developed as a promising candidate for the water window region working near both the Sc-L edge (3.11 nm) and the V-L edge (2.42 nm). To meet the application requirements, its thermal and temporal stability were studied. A series of V/Sc multilayers with a d-spacing ranging from 1.59 to 1.62 nm and a number of bilayers of 100 and 400 was fabricated. Different samples were annealed at temperatures from 100 to 300 °C. Grazing incidence X-ray reflectivity and soft X-ray (SXR) reflectivity measurements showed that the multilayer structure and reflectivity remain mostly unchanged at 100 °C. An obvious deterioration started at 200 °C, while the SXR reflectivity drops close to zero at 250 °C. The multilayer structure completely broke down at 300 °C. Both X-ray diffraction and transmission electron microscopy measurements demonstrated a severe crystallization occurring at 250 °C. Energy dispersive X-ray spectroscopy measurements have further confirmed a significant elemental mixture occurring after 250 °C annealing. The severe intermixing and polycrystallization resulted in the degradation of the multilayer structure. On the other hand, the V/Sc multilayer is relatively stable after half year storage in air environment showing a slight decrease of SXR reflectivity from 18.4% to 16.5%.