In recent decades, shake table real-time hybrid simulation (RTHS) has emerged as a promising seismic testing approach for complex engineering structures. However, the current shake table RTHS systems with actuators typically install the dynamic actuators on a reaction wall outside the table, which introduce interaction issues between the dynamic actuators and the shake table. This study proposes a potential improvement by developing a shake table RTHS platform with onboard actuators. The platform incorporates a 6 m × 9 m large-scale shake table where the physical substructure, two dynamic actuators, and the reaction frame are all positioned. To validate the effectiveness of the developed platform, a two-story steel frame is tested by both full structure shake table test and substructure shake table RTHS. In the shake table RTHS, the lower part of the frame serves as the physical substructure and is simultaneously loaded by the shake table and dynamic actuators, while the upper part is numerically analyzed in OpenSees, using OpenFresco and Simulink as intermediate softwares. The test results demonstrate that the developed shake table RTHS platform provides reasonable predictions to the structural seismic responses. In addition, time delay is optimized using both inner and outer loop compensators, highlighting the effectiveness of inverse compensation and adaptive time series (ATS) compensation schemes. This paper successfully develops a shake table RTHS platform using a large shake table with onboard dynamic actuators, providing a valuable seismic testing platform for RTHS of large-scale complex engineering structures.