Spherical storage tanks are widely used for various types of liquids, including hazardous contents, thus requiring suitable and careful design for seismic actions. On this topic, a significant case study is described in this paper, dealing with the dynamic analysis of a spherical storage tank containing butane. The analyses are based on a detailed finite element (FE) model; moreover, a simplified single-degree-of-freedom idealization is also set up and used for verification of the FE results. Particular attention is paid to the influence of sloshing effects and of the soil–structure interaction for which no special provisions are contained in technical codes for this reference case. Sloshing effects are investigated according to the current literature state of the art. An efficient methodology based on an “impulsive–convective” decomposition of the container-fluid motion is adopted for the calculation of the seismic force. With regard to the second point, considering that the tank is founded on piles, soil–structure interaction is taken into account by computing the dynamic impedances. Comparison between seismic action effects, obtained with and without consideration of sloshing and soil–structure interaction, shows a rather important influence of these parameters on the final results. Sloshing effects and soil–structure interaction can produce, for the case at hand, beneficial effects. For soil–structure interaction, this depends on the increase of the fundamental period and of the effective damping of the overall system, which leads to reduced design spectral values.