The design of a mooring system for a floating structure is a significant challenge: the choice of line structure and layout determine highly nonlinear hydrodynamic behaviors that, in turn, influence the dynamics of the whole system. The difficulty is particularly acute for floating Wave Energy Converters (WECs) as these machines rely on their movements to extract useful power from wave motions – the mooring must constrain the WEC motion without detracting from power production. To evaluate candidate mooring layouts, a high fidelity representation of the mooring hydrodynamics may be necessary to capture the salient hydrodynamic properties. Unfortunately, high-fidelity modeling tends to be very computationally expensive, and for this reason previous simulation based mooring design largely relies on simplified representations that only reflect part of the mooring design space since some physical and hydrodynamic properties are dropped. In this work, we present how a full hydrodynamic time domain simulation can be utilized within a Metamodel-Based Optimization to better evaluate a wider range of mooring configurations spanning the breadth of the full design space. The method uses a Metamodel, defined in terms of the mooring physical parameters, to cover the majority of the optimization process – the high fidelity model is used to establish the Metamodel in a pre-processing stage. The method was applied to a case study of a two-body heaving point absorber. It was shown that for a two-body self-reacting WEC the mooring loads can have a significant impact on the relative movements of the two bodies and therefore the efficiency of the device. Compared with previous studies on single body WECs, the mooring lines seems to have a bigger impact for self-reacting WEC.