Inconel alloy 718 is a high-strength and corrosion resistant alloy that is commonly used as a beamline vacuum window. The accumulation of irradiation-induced damage substantially decreases the window’s service lifetime, and replacing it engenders significant beamline downtime. With this application in mind, herein we examine whether post-irradiation annealing can alleviate irradiation-induced damage of Inconel alloy 718. Inconel alloy 718 was received in a solution annealed state. We then irradiated samples using two different modalities (1.5 MeV H+ and 5 MeV Ni2+) at three representative temperatures for beamline windows (room temperature, 100 °C, and 200 °C), followed by annealing at temperatures viable for in-situ annealing processes (no anneal, 300 °C, and 500 °C). Using nanoindentation, we determined that irradiation-induced hardening occurs but is largely mitigated by post-irradiation annealing. Overall, our results suggest that in-situ annealing of radiation damage in Inconel alloy 718 vacuum windows appears feasible, which could potentially decrease beam downtime and maintenance costs.