Development of structural materials for service under extreme conditions is slowed by the lack of high-throughput test protocols. Here, a method that integrates high-throughput nanoindentation mapping with precise temperature control under a vacuum atmosphere is demonstrated. High-entropy alloys (HEAs) may possess the strength and stability required of high-temperature structural materials in next-generation nuclear applications. These alloys, including the compositional variation AlxFeCrNiMn (x = 0, 0.3, 1) presented in this work, have distinct microstructural morphologies, and nanoindentation mapping reveals the mechanical behavior of the distinct phases as a function of temperature up to 400°C. FeCrNiMn (Al = 0) consists of a face-centered cubic (FCC) matrix with body-centered cubic (BCC) precipitates and exhibits significant softening in both phases at elevated temperature. In contrast, both the FCC phase and FCC–BCC phases present in Al0.3FeCrNiMn show approximately 90% retention of the room temperature hardness at 400°C, and AlFeCrNiMn with BCC and B2 structures shows a similar 85% retention of hardness.