Blanching is a necessary stage in fruits and vegetable processing to inactivate enzymes and destroy microorganisms but, can degrade heat-sensitive nutrients. Therefore, in this study, the vacuum infusion of black cherry tomatoes (Solanum lycopersicum cv. OG) was optimized to obtain the highest blanching efficiency while maintaining maximum levels of bioactive compounds. The experiment was designed using the Response Surface Methodology (RSM) with two factors of vacuum level (529-671 mmHg) and treatment time (16-24 mins). The research found that the optimum vacuum level and processing time, 620.70 mmHg and 22.27 mins, respectively, gave the best results with the weight gain 2.33% after vacuum infiltration, the remaining peroxidase activity 12.24% db and the pectin content 36.55% db after blanching at 90oC for 60 . Meanwhile, the remaining peroxidase activity and pectin content were 30.98% db and 16.86% db, respectively for the 1st-control sample (not vacuum treated and blanched at 90oC for 60 s). The content of lycopene, vitamin C and total phenolic in vacuum infiltrated sample (66.32 mg/100 g db, 0.762% db, 6.42 mg GAE/g db, respectively) was lower than the 1st-control (73.82 mg/100 g db, 1.01% db, 6.55 mg GAE/g db, respectively) but higher than the 2nd-control (not vacuum treated and blanched at 90oC for 80 s attaining equivalent remaining peroxidase activity of 12.51%) (62.26 mg/100 g db, 0.710% db, 5.70 mg GAE/g db, respectively) due to heat transfer efficiency. However, there was no difference between the samples with and without vacuum treatment at the same blanching condition s for anthocyanin content because this compound was found predominantly in outer cell layers. This suggested that the vacuum infiltration helped to inactivate the peroxidase as well as create soluble pectin more but maintain the content of bioactive compounds, especially anthocyanin.