High carbon emissions have shown a strong correlation with rising global temperatures as the world's climate undergoes a dramatic shift. Work to mitigate the potential damage using materials such as metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and polymer membranes (PMs) has proven successful in small-scale approaches; however, research is still being performed to enhance the capabilities of these materials for use at an industrial scale. One strategy for increasing performance is to embed these materials with CO2-philic molecules, which enhance selective binding over other gases. Calixarenes are promising candidates due to their large chalice shape, which allows for the possibility to bind multiple CO2 molecules per site. In this study, a dataset including 40 functionalized calixarene structures and one unfunctionalized (bare) calixarene was constructed with an automated, high-throughput structure generation through directed modifications to a molecular scaffold. A conformational search based on molecular mechanics allowed the faster determination of optimal binding energies for a vast array of chemical functional groups with less computational effort. Density functional theory and symmetry-adapted perturbation theory calculations were performed for the exploration of their interactions with CO2. Our work has identified new organic cages with increased CO2-philicity. In four cases, CO2 binding is stronger than 9.0 kcal/mol and very close to the targets set by previous studies. The nature of the noncovalent interactions for these cases is analyzed and discussed. Conclusions from this study can aid synthetic efforts for the next generation of functional materials.