This paper presents a parametric numerical study aiming to explore the in-plane lateral behavior of concrete sandwich panel-infilled steel frames (CSP-ISF) through a non-linear finite element (FE) method. After validation of the numerical models against experimental data, the effect of parameters, such as compressive strength and thickness of the shotcrete, stiffness of the frame, magnitude of the vertical load, and the size of a central opening, was investigated. It was found that the presence of an opening in the infill and the frame’s stiffness have the most significant effects. As the frame’s stiffness increased, the lateral stiffness and strength of CSP-ISFs increased by roughly 25–45% for the infilled frames with different aspect ratios. Applying gravity load on the top beam increased the shear resistance and the lateral stiffness. However, increasing vertical loads on columns (up to about 30% of their axial capacity) did not affect the in-plane behavior of CSP- ISFs. With an increase in the level of the vertical load on the top beam, the improvement of the initial stiffness and in-plane shear capacity of CSP-ISFs varied between 2 to 25% and 10 to 50%, respectively (for various aspect ratios). A central opening in the infill led to a reduction in the lateral stiffness and ultimate strength of the entire system. Based on regression analysis on FE results, a simplified analytical method was developed to predict the lateral stiffness and the ultimate strength of CSP-ISFs with a central opening.