With a focus on a number of state-of-the-art techniques in the area of autonomous non-rigid space systems control, realization of a comprehensive strategy is worthy of investigation to handle a set of parameters of the present overactuated processes with model uncertainties. In a word, the subject behind the research is to guarantee the desirable performance of a class of the autonomous space systems, which can be considered through the moments of inertia, the central of mass, the profile of the thrust vector and the misalignments of the propellant engine to deal with mission operation plans. There is the attitude cascade strategy including the low thrust three-axis engine off mode control, the low thrust x-axis engine on mode control and finally the high thrust y,z-axis engine on mode control, respectively. The control strategy is realized in a number of loops, as long as the on and off modes of the propellant engine are focused on the Euler angles control, in finite burn time, and quaternion vector control, in non-burn time, respectively, in line with parameters variations. It is to note that the parameters variations are coherently different in each one of the engine modes. The dynamics of high-low thrusters are taken into real consideration, where the control allocations in association with the pulse-width pulse-frequency modulators are employed to cope with a set of on–off reaction thrusters. The investigated results are finally analyzed in line with some related well-known benchmarks to verify the approach performance. The main contribution and motivation of the strategy investigated here is to propose a novel three-axis comprehensive cascade robust control solution to be able to deal with the parameters of autonomous non-rigid space systems under control with model uncertainties, in a synchronous manner, once the results regarding the tracking of the three-axis referenced commands are efficient with high accuracy along with the recent potential outcomes, researched in this area.