The global shear capacity of steel–concrete composite downstand cellular beams with precast hollow-core units is an important calculation as it affects the span-to-depth ratios and the amount of material used, hence affecting the embodied CO2 calculation when designers are producing floor grids. This paper presents a reliable tool that can be used by designers to alter and optimise grip options during the preliminary design stages, without the need to run onerous calculations. The global shear capacity prediction formula is developed using five machine learning models. First, a finite element model database is developed. The influence of the opening diameter, web opening spacing, tee-section height, concrete topping thickness, interaction degree, and the number of shear studs above the web opening are investigated. Reliability analysis is conducted to assess the design method and propose new partial safety factors. The Catboost regressor algorithm presented better accuracy compared to the other algorithms. An equation to predict the shear capacity of composite cellular beams with hollow-core units is proposed using gene expression programming. In general, the partial safety factor for resistance, according to the reliability analysis, varied between 1.25 and 1.26.