This paper is aimed at developing several control scenarios for vibration suppression of a flexible microsatellite as a multibody system with nonlinear fully coupled dynamics in different but interconnected in-orbit mission phases. The design approach is to exploit different actuators in a single and hybrid configuration with an optimal switching mechanism to achieve a desirable maneuvering performance by means of agility and accuracy. In this regard, a genetic algorithm (GA)-particle swarm optimization (PSO) based nonsingular terminal sliding mode control (GP-NSTSMC) and extended Lyapunov-based controller design (LD) are developed to cope with the limitations of bounded uncertainty and external disturbances. Great features of the GP-NSTSMC are its gains which are selected based on two major criteria, system energy and maneuver time, and for LD we consider the piezoelectric (PZT) and reaction wheel (RW) performance in the form of mechanical and electrical energies in the structure of the control algorithm. Despite the capabilities of these algorithms, they still excite high-frequency flexible modes. Accordingly, by applying feedback voltages to the PZTs, the extra vibration is actively damped, where the strain rate feedback (SRF) method is set to determine the control voltages. Furthermore, to satisfy one of the mission’s requirements, which is solar panels deployment, a classical Levenberg–Marquardt (CLM) technique for online mass property identification along with an effective fault detection scenario is employed. A comparative assessment of the proposed hybrid actuator/controllers is presented to clarify the technical aspects of this multimode scenario for further investigations and practical real-time space missions.