In this study, we investigated the effects of different frying conditions on the quality characteristics of fried Spanish mackerel (Scaberulous niphonius) to address the food quality degradation of self-heating fish products after frying, sterilization, and reheating. Furthermore, the effect of different moisture contents (65%, 60%, 55%, and 50%) of fried Spanish mackerel on texture, color, and microstructure after sterilization and self-heating were examined. The flavor fingerprints of different frying temperatures (140 °C, 160 °C, 180 °C, and 200 °C) coupled with the optimal moisture content were identified; furthermore, volatile organic compounds (VOCs) were studied using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) with principal component analysis (PCA). The results indicated that the shear force value significantly increased, while the hardness and chewiness significantly decreased simultaneously with decreasing moisture content. Samples containing 65% moisture content showed the highest L*, a*, and W values, while their b* value was the lowest, and the most clearly visible fibrous veins with tiny cracks could be observed in them. Samples fried at 160 °C and 65% moisture content exhibited the richest VOCs, with a greasy or fried aroma. Based on the PCA, there were significant differences in the sample VOCs under different frying conditions. In summary, among all treatments, frying at 160 °C with 65% moisture content resulted in the highest food quality of fish filets. The results of this study could provide a theoretical basis for improving the food quality of self-heated fish products.