Disclosed herein are embodiments of heat spreaders with interlocked inserts, and related devices and methods. In some embodiments, a heat spreader may include: a frame formed of a first material, wherein the frame includes an opening, a projection of the frame extends into the opening, and the projection has a top surface, a side surface, and a bottom surface; a recess having at least one sidewall formed by the frame; and an insert formed of a second material different from the first material, wherein the insert is disposed in the frame and in contact with the top surface, the side surface, and the bottom surface of the projection.