Nowadays, there has been a growing interest in understanding earthquake forerunners, i.e., anomalous variations that are possibly associated with the complex process of earthquake evolution. In this context, the Robust Satellite Technique was coupled with 10 years (2012–2021) of daily night-time MODIS-Land Surface Temperature remote sensing data to detect thermal anomalies likely related to the 27 September 2021, strong onshore earthquake of magnitude Mw6.0 occurring near the Arkalochori village in Central Crete, Greece. Eight intense (signal-to-noise ratio > 3) and infrequent, quite extensive, and temporally persistent thermal signal transients were detected and characterized as pre-seismic anomalies, while one thermal signal transient was identified as a co-seismic effect on the day of the main tectonic event. The thermal anomalies dataset was combined with tectonic parameters of Central Crete, such as active faults and fault density, seismogenic zones and ground displacement maps produced using Sentinel-1 satellite imagery and the Interferometric Synthetic Aperture Radar technique. Regarding the thermal anomaly of 27 September, its greatest portion was observed over the footwall part of the fault where a significant subsidence up to 20 cm exists. We suggest that the thermal anomalies are possibly connected with gas release which happens due to stress changes and is controlled by the existence of tectonic lines and the density of the faults, even if alternative explanations could not be excluded.