The invention discloses a double-VGT two-stage supercharged diesel engine variable altitude simulation test system and method. The double-VGT two-stage adjustable supercharged diesel engine variable altitude simulation test system comprises an environment pressure simulation system, an engine power measuring system, a combustion analysis system, a calibration system, a high-pressure stage VGT, namely, an HVGT, a low-pressure stage VGT, namely, an LVGT, a diesel engine control unit ECU and a supercharger control unit TCU, the ECU controls the oil injection quantity, the oil injection advance angle and the common rail pressure in real time, and the TCU controls the blade opening degree of the high-pressure stage VGT and the blade opening degree of the low-pressure stage VGT. According to the method, under the conditions of variable altitudes and variable working conditions, based on the optimal MAP of oil injection parameters and pressurization control parameters obtained through coupling optimization of a neural network and a genetic algorithm, an eight-factor and three-level orthogonal test is designed, and a two-stage pressurization and oil injection parameter variable-altitude collaborative calibration test is carried out. Oil-gas-chamber optimal matching of a 0-5500 m diesel engine is achieved, and the variable altitude and variable working condition dynamic property and economical efficiency of the diesel engine are greatly improved.