This article presents the design, analysis, and prototype testing of a four-degrees-of-freedom (4-DoFs) spatial pose adjustment system (SPAS) that achieves high-precision positioning with 4-DoFs (Z/Tip/Tilt/Θ). The system employs a piezoelectric-driven amplification mechanism that combines a bridge lever hybrid amplification mechanism, a double four-bar guide mechanism, and a multi-level lever symmetric rotation mechanism. By integrating these mechanisms, the system achieves low coupling, high stiffness, and wide stroke range. Analytical modeling and finite element analysis are employed to optimize geometric parameters. A prototype is fabricated, and its performance is verified through testing. The results indicate that the Z-direction feed microstroke is 327.37 μm, the yaw motion angle around the X and Y axes is 3.462 mrad, and the rotation motion angle around the Z axis is 12.684 mrad. The x-axis and y-axis motion magnification ratio can reach 7.43. Closed-loop decoupling control experiments for multiple-input-multiple-outputs (MIMO) systems using inverse kinematics and proportional-integral-derivative feedback controllers were conducted. The results show that the Z-direction positioning accuracy is ±100 nm, the X and Y axis yaw motion accuracy is ±2 μrad, and the Z-axis rotation accuracy is ±25 μrad. Due to the ZTTΘ mechanism, the design proved to be feasible and advantageous, demonstrating its potential for precision machining and micro-nano manipulation.