This work presents an advanced structural reliability analysis of circular concrete-filled steel tubular (CFST) members through machine learning and global optimization, together with numerical Monte Carlo simulations (MCS). The artificial neural network (ANN) model is developed and validated against available experimental data. On the basis of monetary cost of materials, the optimal design of CFST members with reliability constraint is formulated and solved by balancing composite motion optimization (BCMO) algorithm. Based on the MCS, reliability analysis is then carried out to calculate the coefficient of variation of optimal design under different loads. Subsequently, a comprehensive prediction simulation, taking account of the uncertainty of experimental data and potential errors from models (ANN, MCS, and BCMO), is performed to generate the statistics on the axial capacity of CFST members. The critical value for the optimal solution is also investigated as a function of the input variables. The results of this study can be applied to achieve a better reliability-based design optimization with minimum cost for the circular CFST columns.