Regional transportation operations centers (TOCs) are at the core of managing and operating a complex surface transportation system. To ensure reliable transportation services, particularly during emergency situations when transportation is vital, uninterrupted operations of TOCs should be guaranteed. Achieving TOC interoperability is of great importance. Interoperability of TOCs can be understood as the ability of one TOC to access and manage some set of the resources of another (remote) TOC. TOC interoperability can allow each metropolitan area or in some cases each state to achieve more robust and seamless interregional operations. In addition, interoperability may provide each region with a better understanding of each partner's practices and thus promote more consistent and coordinated transportation systems operations. Although these benefits are compelling, TOC interoperability cannot be easily established because of the complex technical and institutional situations of existing centers. Given this background, this study explored various operational concepts and developed a methodology to achieve interregional TOC interoperability. The methodology consists of four steps: (a) develop an emergency backup plan for each TOC, (b) establish relationships among TOCs, (c) develop a communications network, and (d) establish institutional interoperability between designated TOCs. In a case study, the proposed methodology was applied to the five regional TOCs in the Commonwealth of Virginia.