To improve the figure of merit (ZT) of thermoelectric (TE) materials, the decoupling of the power factor and thermal conductivity, which are mutually dependent on each other in the traditional TE materials, is desired. The chalcogenides are one of the typical TE materials. When the chalcogenide TE materials are made from nanostructures, large interface density would apparently result in a low thermal conductivity. Additionally, the power factor of the chalcogenide TE materials can also be improved by some modification of their electronic structures. The bottom-up solution-processed synthesis to prepare the nanostructured chalcogenide TE materials is versatile, simple, low-cost, and compatible with the scale-up manufacture and printed flexible electronics. In this progress report, first, the techniques used to improve the ZT of chalcogenides with nanostructures are summarized. Subsequently, the chemical strategies to enhance the ZT are summarized. Finally, the interface and microstructure engineering concepts are concluded, which are crucial to improvement of the ZT of the chalcogenide TE materials from the solution-processed nanostructures.