Nowadays, many high-rise buildings are constructed from concrete-filled steel tubular (CFST) columns and concrete-filled steel plate (CFSP) shear walls due to their superior merits. However, these composite buildings are still designed by traditional load and resistance factor design (LRFD) approach which is conservative and impossible to explicitly capture the complex behaviour of CFST structures. Hence, this paper develops an efficient framework for the system design of CFST structures utilizing nonlinear simulation and reliability analysis. Firstly, a C+ + source code for a new material model is developed in OpenSees to capture the behaviour of semi-rigid connections. This material is implemented into the numerical model of CFST structures. Secondly, a framework based on subset simulation is developed for the reliability analysis. This code rigorously considers uncertainties of variables such as numerical model, geometric and material properties or applied loads of both American (US) and Australian (AS) standards. Finally, case study and parametric study are conducted by using the developed framework to propose resistance reduction factors for the investigated frames. The results of the study show that the resistance reduction factor can be taken as 0.8 for both AS and US codes. This proposed factor can be a great source of reference for the system design of CFST buildings with composite shear walls.