Base isolation is a widely recognized strategy for mitigating seismic demands in structures, effectively enhancing safety by reducing inertial forces and limiting structural damage. However, its application in near-fault sites, defined as sites located within approximately 15 km of a fault, necessitates additional considerations due to the distinctive characteristics of near-fault ground motions, which are not yet comprehensively addressed by current seismic design codes. Extensive research has shed light on the distinctive characteristics of near-fault ground motions, particularly the pronounced effects of forward directivity in the horizontal component and significant vertical accelerations, especially near dip-slip faults. The former often results in large, long-period velocity pulses that critically influence the displacement demand on base-isolated systems, especially as isolation periods increase. Concurrently, the vertical component of near-fault ground motion, especially in the presence of dip-slip fault mechanisms, may exhibit vertical-to-horizontal spectral acceleration ratios (V/H) exceeding unity at short periods (0.05–0.10 s), with amplified effects in soft soil conditions. While the influence of vertical excitations on vertical-sensitive structures has been previously investigated, their implications for base-isolated systems remain insufficiently explored. This study examines the seismic response of base-isolated buildings employing High Damping Rubber Bearings (HDRBs), both independently and in combination with low-friction Flat Slider Bearings (FSBs), when subjected to near-fault seismic inputs. Utilizing recent Ground Motion Models specifically developed for near-fault scenarios, horizontal and vertical design response spectra were derived and employed within the Eurocode-based design framework. The results underscore the critical influence of fault proximity, with reduced distances leading to markedly increased displacement demands, necessitating substantial isolator volumes and a higher quantity of FSBs to achieve target performance. Furthermore, vertical ground motion was found to significantly impact the compressive and tensile behaviour of isolation devices, potentially inducing uplift in sliders and overstressing HDRBs, thereby reinforcing the imperative to incorporate vertical effects in the seismic design of isolated structures located near active faults.