Concerning the use of modern technologies and manufacturing systems in the production of high-stress components from Ni-base superalloys and the optimization of the production process, knowledge of the microstructure–mechanical properties relationship is very important. The microstructure of Ni-base superalloys is very closely related to the chemical composition. With the high number of alloying elements, various phases are presented in the structure of Ni-base superalloys, which have a predominantly positive effect on the mechanical properties, but also phases that reduce, in particular, the heat resistance of these materials. The aim of the presented paper is the quantification of structural parameters of two types of cast alloys, ZhS6K and IN738, where the effect of dwell at 10 and 15 h at 800 °C on the change in morphology and volume fraction of the γ′-phase precipitate was studied. The detected changes were verified by the Vickers hardness test. The IN718 superalloy was chosen as a representative of the wrought superalloy. This alloy was also annealed for 72 h at a temperature of 800 °C, and the quantification of structural parameters was performed by EDS mapping and TEM analysis. Another partial goal was to assess the effect of changes in the volume fraction of the γ′-phase and δ-phase on the change in the high-cycle fatigue life of superalloy IN 718. This superalloy was tested by dynamic cyclic loading with cycle asymmetry parameter R = −1 at an ambient temperature of 22 ± 5 °C and at a temperature of 700 ± 5 °C and with cycle asymmetry parameter R < 1 (three-point bending load) after annealing at 700 °C/72 h. The results of the quantitative analyses and fatigue tests will be further used in optimizing the design of Ni-base superalloy components by modern technologies such as additive technologies for the production of turbine blades and implemented within the philosophy of Industry 4.0.