Evolution of an initial nearly-lamellar (γ+α2+β0) structure of a new cast β-solidifying TiAl-based alloy Ti-44.5Al-2V-1Nb-2Cr-0.1Gd (at.%) after isothermal exposures at 800 °C for up to 10,000 h has been systematically investigated using SEM, TEM, EDS, and XRD analyses. During the exposures the alloy microstructure degraded by the α2 laths and β0 phase dissolution, resulting in coarsening of lamellar structure and rising of the γ phase volume fraction. A 2.5- and 3-fold increase in the number of nano-sized gadolinium oxide (Gd2O3) particles have been observed after 10,000-h exposure in lamellar colonies and in grain boundaries, respectively. The gadolinium oxides had monoclinic (C2/m) and cubic (Ia-3) structures and precipitated predominantly along γ/α2 and γ/β0 interfaces and inside the γ lamellae. Furthermore, the applied creep loading was found to contribute significantly to the precipitation process of Gd2O3 nano-particles, since dislocation networks being the sites for their preferred formation. Nanohardness of the γ phase increased from 4.4 ± 0.3 to 5.0 ± 0.4 GPa after the exposures, but no changes were observed for the β0 phase. As a result of structure evolution the tensile strengths reduced by 10–12 and 11–14 % measured at 20 and 750 °C testing temperatures, respectively. Meanwhile, the plastic elongation values remained essentially unchanged. We interpret this as insignificant effect of the precipitation of Gd-rich oxide nano-particles on the alloy ductility.