Abstract: Sous vide technology has widely served as a series of pre-cooked food products in recent years. This study aims to investigate the specific impact on the quality of salmon, in order to explore the feasibility and potential of sous vide salmon. The quality indicators of salmon were measured using sensory evaluation and microstructural analysis, including the juice loss rate, major nutrient content, fatty acid composition, lipid oxidation, and protein degradation. A series of experiments were conducted under various cooking temperatures (38, 46, 54, and 62 °C), the durations (10, 25, 40, and 55 mins), and the vacuum levels (0.100, 0.050, and 0.025 MPa) under atmospheric pressure. A systematic investigation was further made to explore the impact of temperature on the key lipid molecules after oxidation using lipidomics. The results show that: There was an increase in the brightness, juice loss rate, hardness, total protein content, POV (peroxide value), and TBARS (thiobarbituric acid reactive substances) value of salmon samples, as the cooking temperature increased. While there were also intensified values in the sensory score, total fat content, and degradation of myosin and actin. Among them, the sensory score of odor indicators first increased and then decreased, as the temperature rose. The extending cooking duration led to an increase in the brightness, yellowness value, juice loss rate, elasticity, and hardness, along with a decrease in the sensory score (due to the decreased color, tenderness, texture, and resilience). The content of saturated fatty acids first increased and then decreased, while the content of polyunsaturated fatty acids decreased, accompanied by degradation of myosin heavy chains. The HE staining and electron microscopy showed that the muscle fibers were tightly packed with the increase in cooking temperature. The muscle fibers were destroyed when the temperature was too high. The total fat content rose under high vacuum. While there was a relatively minor impact on the sensory quality, fat oxidation, and actin degradation, resulting in the lowest POV and TBARS values. Lipidomics analysis indicated that the higher temperatures led to more significant changes in the lipid molecules in salmon samples, indicating an upward trend with amplified differences. The total content of oxidized phospholipids was gradually accumulated, as the temperature elevated. Vacuum cooking at lower temperatures reduced the formation of oxidized phospholipids, indicating the outstanding effectiveness of vacuum low-temperature slowed cooking with high-quality salmon. Consequently, the steaming temperature shared the most significant impact on the quality of salmon, followed closely by steaming duration and vacuum level. The sous vide technique can be expected to combine the low temperature and vacuum, in order to effectively minimize the oxidized phospholipids and lipid oxidation in salmon. The superior quality and sensory attributes of salmon were preserved to evaluate the quality indicators after processing. The optimal parameters of this sous vide process were obtained: the steaming salmon at a temperature of 46 °C for 25 min under a high vacuum of 0.100 MPa, resulting in a relatively excellent quality and sensory experience. The findings can provide comprehensive data support and a robust theoretical foundation to optimize the sous vide technology for high-quality salmon products. In turn, their market value can ultimately contribute to the sustainable industry.