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Due to many advantages, such as cost-effective production, design freedom, and weight reduction, plastics have replaced metals and ceramics in many fields. However, engineering plastics are good thermal insulators. This characteristic, although beneficial in certain applications, poses many challenges in many heat-generating applications. This can lead to hot spots or even to an increase in the device temperature. Along with the increasing demand for plastics in areas of the lighting technology or in the automotive field due to the free shaping potential, the requirements are becoming more challenging. Driven by the trend of miniaturization, applications with high heat generation often have to operate in the tightest of spaces. Since not always sufficient space for complex cooling systems is given, the housing or the substrate should assume the task of thermal management. In regard to this fact, the use of thermally conductive thermoplastics seems to be very appealing. Quality loss, poorer reliability, loss of performance, and even failure can occur in case of insufficient heat dissipation. In order to improve the properties of these polymers, highly heat-conducting fillers are added in order to improve the thermal conductivity of the compound. Another technology trend that has been prevalent for years is the use of simulations. Due to shorter product life cycles and therefore shorter development times, simulation has become an indispensable part of the chain of product development. Timeconsuming and costly test series make the simulation more and more important as a tool for material and product design. In this context, this paper presents a novel approach for reliability investigation and lifetime estimation, based on simulation. Therefore, a simulative method based on coupling the results from the process simulation (injection molding simulation) to finite element analysis was developed and explained. This coupled method makes it possible to take into account the manufacturing process and its engendered filler orientation. The obtained findings are compared to conventional thermal steady-state analysis and used in order to better predict the lifetime of LEDs mounted on thermoplastic substrates, the so-called molded interconnect devices. It is demonstrated that it is necessary to consider the filler orientation, especially in the case of 3D substrates.