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Network mobility (NEMO) basic support protocol is designed to support network mobility management, and it ensures communication continuity for nodes in the mobile networks. However, NEMO in nested mobile networks suffers from the pinball routing problem, resulting in the long packet transmission delay. Therefore, we propose a domain-based route optimization (DRO) scheme that incorporates the domain-based network architecture and the operations of ad hoc routing protocols to perform the route optimization. Moreover, DRO improves the inter-domain and intra-domain handoff performance. Detailed performance evaluation is performed via comparisons with existing route optimization schemes. From the analysis results, we can see that DRO can achieve low packet transmission delay (i.e., better route-optimization) and low handoff latency.