Additive manufacturing (AM) can be particularly advantageous to manufacture components designed to meet challenging structural requirements. Selective laser melting (SLM) microstructure is different than that obtained by traditional manufacturing process; in particular, mechanical and microstructural features achieved herein are influenced by the entire thermal history, including the manufacturing process and the heat treatment (HT) with relevant role of the slow cooling rate adopted. In fact, both the process and the HTs can significantly modify the microstructure and related mechanical and tribological properties. To better understand how mechanical response can be tuned to meet different requirements, in this article the effects of four different vacuum HTs on microstructures, mechanical properties, and wear behavior of Inconel 625 produced with SLM are deeply investigated. In general, the results confirm that HT can significantly change the microstructure and mechanical or tribological properties of Inconel 625. Among the examined HT, solution + aging and direct aging improve the strength of the alloy, whereas annealing leads to recrystallization, reducing strength in favor of ductility. Stress relieving does not significantly change the microstructure and mechanical properties. Considering tribological behavior, only direct aging HT leads to a remarkable improvement, with a reduction in friction coefficient and wear rate.