In this work, the sensitivity zone of microstructure and temperature for precipitation-strengthened nickel-based superalloys, used for turbine applications in aero-engines, has been firstly established. Heat treatment experiments with different solution temperatures were carried out. The microstructure evolution and creep residual strain sensitivity, low cycle fatigue properties, and tensile properties are analyzed, and the essential reason for the fluctuation of the mechanical properties of nickel-based superalloys was revealed. The main results obtained are as follows: following subsolvus solution heat treatment with a temperature of 1020 °C, samples have a high primary γ′I phase content, which is beneficial to low creep residual strain. Above the supersolvus solution temperature of 1040 °C, the creep residual strain value and low cycle fatigue performance fluctuate significantly. The essential reason for the dramatic fluctuation of performance is the presence of γ′ phases in different sizes and quantities, especially following the solution heat treatment in the temperature-sensitive zone of the γ′I phase, which is likely to cause huge fluctuations in the microstructure of tertiary γ′III phases. A zone of particular sensitivity in terms of temperature and microstructure for the γ′I phase is proposed. The range of suitable solution temperatures are discussed. In order to maintain stable mechanical properties without large fluctuations, the influence of the sensitivity within this temperature and microstructure zone on the γ′ phase should be considered.