The hybrid thermal-chemical method of nanocatalytic aquathermolysis is one of the newest methods, which is proposed to enhanced oil recovery (EOR) from heavy oil reservoirs. To operationalize and optimize this method in oil fields, it is necessary to know the influencing parameters and investigate the interaction between them. Therefore, in this study, interactions among oil type, residence time, and temperature parameters on the nanocatalytic aquathermolysis process are studied by simulating the kinetic of chemical reactions during fluid flow in a large scale porous media and by utilizing of central composite design (CCD) statistical method. To accomplish this, all reactions are analyzed and compositional changes in oil, along with changes in density, viscosity, and cumulative production of oil are monitored over time. Finally, single-objective optimization with the main goal of increasing oil recovery and multi-objective optimization with the aim of reducing temperature and residence time besides increasing oil recovery is carried out. Temperature and oil type have the most interaction, and residence time and oil type have the least interaction. At high temperatures, the upgrading process is more effective on lighter oil, while at low temperatures, the process is more effective on heavier oil. Also, the optimum temperature in heavier oil is lower than in the lighter oil. A longer residence time increases production at lower temperatures, and inversely at high temperatures, increasing the residence time causes a decrease in production. Also, residence time has a greater influence on lighter oil relative to heavier oil in lower temperatures, and conversely, residence time has a greater effect on heavier oil than lighter oil at higher temperatures. In single-objective optimization, 334.79 °C, lighter oil and almost 0 months, and in multi-objective optimization, 180.47 °C, heavier oil and 0 months were the optimum upgrading condition. In these conditions, cumulative oil production was about 39,829 and 31,593 STB, respectively. • Kinetic analysis of binary interactions of oil type, residence time and temperature parameters. • Details on how to carry out reactions, changes in oil components over time, changes in density and viscosity, and changes in cumulative production of oil. • Single-objective optimization with the main goal of increasing oil recovery and multi-objective optimization with the aim of reducing temperature and residence time besides increasing oil recovery. [ABSTRACT FROM AUTHOR]