The compressor inter-spool duct (ISD), with its offset and profiled curvature, is an inherent part of the turbofan system due to large density gradients and substantial area changes across each spool. The aerodynamic performance of the ISD is highly dependent on the upstream flow conditions, and hence its design process must account for the upstream effects. In the present investigation, the inter-spool duct design is carried out, suiting an existing high-speed transonic compressor stage, forming an integrated system. The emphasis of this investigation is to assess the effect of upstream secondary flow structure, i.e., shock losses, tip leakage vortices, blade wakes, and corner-separated flow, on the aerodynamic performance of the duct. The compressor stage performance is presented with the help of experimental and numerical data at design and off-design conditions. The inter-spool duct is numerically analyzed considering uniform inlet flow and the flow coming from the upstream high-speed compressor stage. This investigation reveals that the duct with uniform inlet flow is free from any severe flow separation; consequently, minimum loss. However, the losses are observed to increase significantly with the upstream compressor stage. The majority of the losses are incurred at the duct inner wall due to large wake structures emanating from the stator hub section. The stage exit swirl throughout the duct in the outer wall region, in combination with the hub-separated flow, results in the low-pressure region at the duct-inner wall, causing flow reversal at the exit. This creates flow blockage resulting in a decrease in the choke margin of the integrated system. The overall efficiency of the integrated system is also reduced owing to the losses encountered within the duct.