While one salient characteristic of hub airports lies in connecting passengers, the full-service airlines in North America concentrate their networks spatially over a number of hubs. Having witnessed the emerging multi-hub network, this paper investigated the flight scheduling problem under a multi-hub configuration, taking a well-defined bank structure and airport operational restrictions into account. An integrated non-convex Mixed-Integer Nonlinear Programming (MINLP) approach was proposed to enhance airline connectivity, considering different combinations of traffic flow direction and connecting times. To verify the scalability and effectiveness of the proposed model, a comprehensive case study has been undertaken with real-world scheduling data from Air China, which was solved by a novel problem-specific Selective Simulated Annealing (SSA) algorithm. Substantial improvements were achieved without sacrificing the scheduling efficiency. Precisely, the programme adjusted the flights during a typical operational day in a timely manner. The post-optimisation outcomes have witnessed its effectiveness with a 17.97%, 17.06%, 22.41% and 53.86% increase in airline connectivity at its four major hub airports (Chengdu Shangliu, Beijing Capital, Shanghai Pudong and Hongqiao) in China, respectively. A clear pattern of the bank structure also confirms its positive impact on airline connectivity under the multi-hub network configuration. Lastly, a comparative analysis for the distribution of all feasible connections further highlights the critical challenge concerning the role of the hubs in a multi-hub network. More specifically, Air China’s multi-hub network systematically performs better on Domestic-International routes, due to flight schedule, frequencies, geographical placements and detours. Among the four hub airports, Beijing Capital International Airport stands out as a dominant one, which implies its potential to serve as a robust international hub airport.