The development of multi-scale modeling capabilities through the use of coupled system thermal-hydraulic and CFD codes is addressed in this paper, which presents the extension and application of a partitioned, domain decomposition computational method coupling the 1D code RELAP5-3D and the CFD code FLUENT. An implicit coupling scheme for the solution of the flow field, based on a Quasi-Newton algorithm, is developed and tested on a case with multiple coupling interfaces. Moreover, modeling capabilities of the tool are enhanced through the implementation of thermal coupling to compute conjugate heat transfer phenomena. In this work, a coupled model has been developed for the analysis of the pool-type test facility E-SCAPE, currently under commissioning at the Belgian Nuclear Research Centre SCK•CEN. The installation represents a thermal-hydraulic scaled model of the MYRRHA reactor, with an electrical core simulator, cooled by Lead-Bismuth Eutectic (LBE). The coupling tool is applied on the analysis of a total loss of flow (LOF) transient, involving the complex transition from forced to natural circulation flow in the primary system. The simulation results, compared against stand-alone system thermal-hydraulics (STH) simulation data, highlighted that the transient behavior of a pool-type system in natural circulation is characterized by complex multi-dimensional flow and temperature fields, difficult to predict by 1D STH codes. The study also confirmed the capability of the developed tool to predict the impact of such phenomena on the system behavior, and to capture the development of thermal stratification in a plenum at low flow condition. The planned experimental tests will be used for the validation of the tool, in the view of its use for design and licensing activities.