Simulation-based optimization is widely used to improve the performance of an inventory system under uncertainty. However, the black-box function between the input and output, along with the expensive simulation to reproduce a real inventory system, introduces a huge challenge in optimizing these performances. We propose an efficient framework for reducing the total operation cost while satisfying the service level constraints. The performances of each inventory in the system are estimated by kriging models in a region-wise manner which greatly reduces the computational time during both sampling and optimization. The aggregated surrogate models are optimized by a trust-region framework where a model recalibration process is used to ensure the solution's validity. The proposed framework is able to solve general supply chain problems with the multi-sourcing capability, asynchronous ordering, uncertain demand and stochastic lead time. This framework is demonstrated by two case studies with up to 18 nodes with inventory holding capability in the network. (C) 2016 Elsevier Ltd. All rights reserved.