Milli-structured heat exchangers/reactors are one of the intensified technologies, which have been successfully used in the case of exo- or endo-thermal chemical syntheses. Enhanced performances of such technologies compared to conventional apparatuses have been observed. This work is focused on the numerical investigation of the “DeanHex” heat exchanger/reactor with a 2D-meandering square cross-section channel with a hydraulic diameter of 2 mm. Throughout the years, only a part of the corrugated channel had been modelled due to the high ressource consumption of CFD simulations. Therefore, in order to model the reactor in a less resource demanding way than a full 3D approach, a new numerical approach is developed. The 2×2 mm2 meandering flow channel, which is the core of the heat exchanger/reactor design, is depicted by a 1D homogeneous model coupled to a 3D model for the surrounding solid in which the channel is embedded. This offers a compromise between the simulation at small scale and the simulation at the reactor scale, giving a great advantage in computational efficiency over meshing and computing 3D channels. In this paper, the 1D/3D approach is validated with heat transfer calculations between the 1D monophasic flow milli-channel and its 3D surrounding using an experimental work previously conducted on the “DeanHex” heat exchanger/reactor.