In recent years, glass has been a largely used material for load-bearing or non-structural components in buildings and constructions. For this reason, dedicated calculation methods and approaches are required for the major loading and boundary conditions that are of technical interest for safe design purposes. Among others, the resistance and mechanical performance of glass elements under fire exposure still represents an open challenge. This paper elaborates on the failure detection methods for out-of-plane loaded glass panels that are subjected to fire loading and simultaneous mechanical loads. As known, the conventional method for thermal failure detection is based on the maximum temperature gradient in glass, and its comparison with a set of allowable standardized values. However, especially for ordinary glass components in buildings that are required to sustain combined mechanical loads, the overall structural performance is even more complex to predict. This design issue is given to a combination of pure mechanical aspects (i.e., sustained loads and corresponding stress–strain analysis) and thermo-physical phenomena, that depend on the progressive modification of material properties while increasing temperatures. This research study, accordingly, investigates the sensitivity of input parameters on the failure time of a given glass element under fire and sustained mechanical loads. A major advantage is taken from finite element (FE) numerical analyses and standardized failure detection methods of literature, that are selected for comparative purposes. Further, the paper also introduces the “stress approach” that can be used to quantify (in place of the conventional thermal gradient) the actual effects of assigned thermal exposure and mechanical loads.