Thermoplastic resins, such as Liquid Crystal Polymers (LCPs), have many attractive properties for microelectronic cavity package manufacturing (in particular low gas permeation and low dielectric constant). In order to reduce anisotropic mechanical properties inducing a potential fragility of the material and then a lack of reliability of the package, various approaches are currently studied in particular the addition of mineral fillers. A dedicated Design of Experiments (DoE) is performed to assess the optimal thermo-mechanical properties of the LCP compound and then the optimal composition of the package leading to the maximum operating lifetime. In this way the long-term reliability of an electronic package (Quad Flat No-lead – QFN – package) based on various formulations of the LCP composite is assessed by thermo-mechanical simulation using Finite Element Method (FEM). A Design for Reliability (DfR) methodology is proposed according to the simulation results based on Taguchi methodology. This methodology allows the determination of the optimal composition (nature/proportion/size/chemical functionalization of fillers) of the LCP package by reducing the number of experimental studies that are very time consuming.