To determine the optimal reaction conditions of bi-reforming of methane thermodynamic analysis of reaction was performed. The effects of process variables, such as temperature (T = 500–1000°C), pressure (P = 1–30 atm), and feed composition CH4/CO2/H2O on the product distribution were studied. It was shown that to maximize the conversion of reagents and yield of target products the high reaction temperatures (T > 800°C) and atmospheric pressure should be applied. The reaction pathway of the bi-reforming of methane is affected by the feed composition. At 800°C the molar ratio of O/C ≥ 1.1 are preferable to work at region free of carbon formation. The CO2 conversion and H2/CO ratio are controlled by the value of CO2/H2O ratio. Depending on the field of application of synthesis gas, this ratio can be tuned from 1.2 to 2.8 through variation of CO2/H2O ratio from 3 to 0.1. The selected reaction conditions (T = 800°C, P = 1 atm, CH4/CO2/H2O = 1/0.8/0.4) were applied for bi-reforming reaction over Ni catalyst which provided the process parameters close to thermodynamic equilibrium results.