The presence of a fishy odor has emerged as a significant obstacle in the processing and commercialization of tilapia. In light of this, the present study employed ultrasonic-assisted enzyme deodorization to address this issue. The deodorization effects were evaluated from multiple perspectives, including chemical indexes (amino acid nitrogen content, trimethylamine content, and thiobarbituric acid value), physical indexes (texture), and sensory scores. Through the application of response surface methodology, an ultrasound-complex enzyme deodorization (UED) technology was ultimately optimized. The UED process resulted in a 56% reduction in trimethylamine content while also enhancing the taste, odor, and texture of the fish, thereby demonstrating its ability to significantly improve overall quality. Additionally, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC/MS) and gas chromatography-ion mobility spectrometry (GC-IMS) were utilized to comprehensively analyze the impact of UED on flavor and elucidate its deodorization mechanism. Notably, UED samples exhibited reduced levels of components associated with undesirable fishy flavors such as hexanal, nonanal, 1-octen-3-ol, and ethyl propanoate while experiencing an increase in components such as benzaldehyde, cis-Jasmone, and butyl lactate that contribute pleasant fruity and floral aromas. Overall, this study has developed an efficient convenient method for both deodorizing tilapia enhancing its aroma, making valuable contributions towards improving overall flavor profile tilapia products.