Understanding the impact of diverse soil conditions on multi-storied buildings with pile foundations under dynamic loading is pivotal in structural engineering. Soft, medium, and hard soils can markedly affect the structural response to dynamic loads. Traditional design methods often overlook Soil-Structure Interaction (SSI) by assuming a fixed base, which may suffice for low-rise structures on stiff soils but proves inadequate for high-rise structures where SSI plays a more substantial role. The study focuses on investigating variations in structural response due to changes in soil stiffness during earthquakes. Using the finite element (FE) analysis in LUSAS 15.2 software, a 28-storied building frame with shear walls and a pile foundation is analyzed under different soil conditions. Seismic design for high-rise buildings involves calculating seismic base shear (Vb) and design lateral forces based on IS: 1893–2016 standards. The determination of Vb value considers factors like the zone factor, importance factor, response reduction factor, weight of each floor, and fundamental time period (T). For this study, the zone factor, importance factor, and response reduction factor are set at 0.16 (corresponding to zone III), 1.5, and 5, respectively. LUSAS software is utilized to determine the total weight of each story and T. Subsequently, design lateral forces for each floor are calculated based on IS: 1893–2016, considering parameters such as specific floor weight, height from the base, and Vb. The findings indicate higher Vb and design lateral force values in soft soil compared to hard and medium soil conditions. Moreover, design lateral force increases with higher floor levels, particularly in soft soil conditions. Soft soil conditions exhibit a maximum fundamental time period, indicating increased Soil-Structure Interaction (SSI) effects with greater soil flexibility. Additionally, ground response spectra from IS: 1893–2016 are converted into simulated time history data using the TARSCTH code. The synthetic time history response is inputted into DEEPSOIL V 6.1, and deconvolution analysis is performed to obtain the appropriate input motion at a specific depth. This obtained input motion is used in the numerical model, revealing that SSI significantly influences the behavior of buildings on the soil. In summary, this study highlights the importance of incorporating Soil-Structure Interaction (SSI) effects in the design of tall buildings located in seismic-prone regions with soft soil conditions. A comprehensive understanding of these interactions is essential to guarantee the structural integrity and seismic resilience of buildings in such environments.