This paper addresses the integrated circuit industry needs for non-isothermal simulation in device reliability analysis, initial input factor sensitivity analysis and their software implementation. The key reliability issues are the hot-electron induced oxide damages and electro-static discharge (ESD) damages, The main purpose of this work is to provide a design aid tool to improve device reliability and performance. The reliability simulator developed in this work not only predicts designed device reliability, but: also provides some information about the effect of manufacturing variations on reliability. This is accomplished by combining the statistical methodology with existing technology computer aided design (TCAD) tools. The design of experiment (DoE) technique can be successfully employed to analyze the effect of manufacturing variations on the SOH device reliability. As an example, the reliability analysis and the statistical analysis have performed on SOI MOS devices (partially depleted and fully depleted SOI) and submicron bulk-Si MOSFET's to verify the applied modeling method.