Major cities like London, New York, and Tokyo are served by several airports, effectively creating a Multi-Airport System (MAS), or Metroplex. The operations of individual Metroplex airports are highly interdependent, rendering their efficient management rather difficult. This paper proposes a framework for the design of dynamic arrival and departure routes in MAS Terminal Maneuvering Areas, which fundamentally changes the operation in MAS airspaces for much improved efficiency when compared to the current situation. The framework consists of three components. The first presents a new procedure for characterizing dynamic arrival and departure routes based on the spatio-temporal distributions of flights. The second component is a novel Analytic Hierarchy Process (AHP) model for the prioritization of the dynamic routes, which takes into account a set of quantitative and qualitative attributes important for MAS operations. The third component is a priority-based method for the positioning of terminal waypoints as well as the design of three-dimensional, conflict-free terminal routes. Such a method accounts for the AHP-derived priorities while satisfying the minimal separation and aircraft maneuverability constraints. The developed framework is applied to a case study of the New York Metroplex, using aircraft trajectories during a heavy traffic period on typical day of operation in the New York Terminal Control Area in November 2011. The proposed framework is quantitatively assessed using the AirTOp fast-time simulation model. The results suggest significant improvements of the new design over the existing one, as measured by several key performance indicators such as travel distance, travel time, fuel burn, and controller workload. The operational feasibility of the framework is further validated qualitatively by subject matter experts from the Port Authority of New York and New Jersey, the operator of the New York Metroplex.