Seismic fragility, loss and resilience provide a rational basis for decision making in new construction/retrofitting. The inter-storey-isolation (ISI) is a relatively recent seismic vibration control technology for taller buildings. The isolation bearings are placed at an intermediate storey to isolate the upper storey block (USB), which also acts as a non-conventional tuned mass damper (TMD) to the lower storey block (LSB) to reduce the vibration. This study presents the seismic fragility, total expected annual loss ratio (TEALR), the life cycle cost (LCC) and the resilience index (RI) for buildings with ISI. The ISI is shown to considerably reduce the seismic fragility, TEALR and LCC and enhances the RI. Alternative building frames and high damping rubber bearings (HDRBs) are considered to be subjected to a suite of near fault, pulse type ground motions. The reduction in seismic fragility by the ISI system is shown first; followed by the reduction in the TEALR/LCC and enhancement of the RI in respect to the pertinent damage scenarios. A functionality recovery approach is adopted while estimating the RI. These improvements are shown to be maximized by a sufficiently high (nearly 100%) mass ratio (ratio of mass of the upper storey block to the lower storey block) and higher level of viscous damping (e.g. 20%) in the HDRBs. Not only the structural damage(s) but the non-structural and economic damage(s) are also noted to be prominent. Best performances are observed under moderate seismic hazard level but diminishes gradually for extreme hazard, owing to the reduced efficiency of isolation and de-tuning by the incipient nonlinearity.