Due to the little established nuclear desalination plants worldwide, there is lack of technical data and no engough practical experience in coupling field. Therefore, in this study different coupling technologies concerning cogeneration systems for joining nuclear power reactors with large thermal seawater desalination units (MED & MSF) have been reviewed and optimized. A new heat pipes heat exchangers are first proposed for the isolating intermediate loop (IIL), in addition to the previosly reviewed types: flash steam chamber and pressurized water loops. All studied thermal coupling methods are modeled mathimatically as heat exchanger loop transfers safely heat energy from nuclear power plant to desalination plant. A methodology for selecting the optimum coupling system is derived considering several preference indices that mainly depend on IIL characteristics: heat transfer surface area, thermal performance and consumed pumping power.As an exploratory case study, these factors are analyzed and discussed for the SMART reactor type. The results of different thermal coupling schemes for wide range of top brine temperature TBT demonstrate that the heat pipe loop (HPL) is the optimum IIL type and becames the unique inevitable option, due to its attractive and advataguous characteristics for both MED and MSF. Furthermore, from the safety analysis view, the HPL is considered more reliable because the heat pipe itself can represent an additional barrier against product water cotamination. Also, technical guide values of design parameters are concluded from the current model for the design and construction purposes with high accuracy, where the maximum variation not exceed ± 5 % for small and medium nuclear power reactors (SMRs), delivering various power from 50-2000 MW th from backpressure turbine as condenser rating to distillation plants. The present predictions showed also a reasonable agreement when compared with the other literature results for various heat exchangers.