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Hydrothermal alteration can lead to weakening of volcanic rock, decreased slope stability and increased erosion, therefore creating potential mass-wasting hazards at volcanoes. The mechanical weakening may affect rock compounds, selected lithographic layers, or occur along fracture zones, with serious consequences for the evolution of volcanoes. Therefore, understanding the processes and interactions at the intersection of faults and hydrothermal systems is critical for assessing slope instability and the potential for failure. Here, we investigate these interactions at the Profitis Ilias lava dome on Nisyros Island (Greece). Nisyros has a complex volcanic history, including caldera-forming eruptions, extrusion of large rhyodacitic domes inside the caldera, and recurrent high-magnitude seismic activity that continues to shape the island. The most prominent dome, Profitis Ilias, rises up to ~700 m and is located at the intersection of major fault zones and an active hydrothermal system at its base, making it particularly susceptible to alteration-driven weakening. To investigate the impact of hydrothermal alteration on the stability of the dome in this particular setting, we combined optical and thermal satellite and drone-based remote sensing, image analysis, and rock-mechanical field experiments. We used Pleiades data to identify the spatial extent of hydrothermal alteration effects based on rock discolourization, indicative of hydrothermal alteration, by applying Principal Component Analysis. High-resolution optical and infrared drone surveys further constrained the distribution and intensity of hydrothermal activity. Our results show that hydrothermal activity and alteration penetrate deeply into the Profitis Ilias dome, affecting about ⅓ of its surface area. Thermal activity and alteration are observed laterally 500 m away from the eruptive centres at its base into the dome, and up to 300 m altitude above the caldera floor. A comparison with other hydrothermal areas within the caldera reveals that, although features such as Stefanos crater are visually prominent and frequently studied, hydrothermal activity at the base of Profitis Ilias is more extensive and exerts a strong impact on rock integrity. The affected part of the dome exhibits enhanced erosion and morphological evidence of weakening and destabilisation. To evaluate this, we performed rock mechanical field tests employing a Schmidt hammer and sampled rocks to measure their petrophysical and mineralogical properties in the laboratory. Rock mechanical field tests of representative endmember samples from fresh to altered dome rocks generally show strength reductions by over 66% for altered material. Similar measurements along transects at the eastern base of Profitis Ilias flank reveal the same significantly reduced strength relative to fresh dome rock, confirming substantial mechanical weakening of the dome's base. Considering the current deformation pattern on Nisyros, which outlines Profitis Ilias dome in the southeast and northeast along the main tectonic trend and the Mandraki fault, further investigation of dome stability is warranted. In particular, the combined effects of seismic activity, fault movement, and hydrothermal circulation beneath the eastern flank of Profitis Ilias may pose an elevated risk of slope instability.