Design complexity of high-performance electronics systems, including chip-package- board and mechanical surrounding, has dramatically increased in the past years. Due to the growing integration of high-speed digital features (HDMI2.0, USB3.1, LP/DDR4, CPU), reaching compliance with EMI/EMC standards (Electro-Magnetic Interferences and Compatibility) has become challenging. Moreover EM co-existence issues with RF wireless / analog interfaces (WiFi, Bluetooth, ZigBee) can potentially occur, causing integrity problems and bandwidth reduction. In some cases, fixing the EMI/EMC issues requires a re-design of the product and delays mass-production. This paper presents the challenges and the achievements in the development of a new simulation methodology to estimate, investigate and address radiated EMI/EMC/Co-existence issues. The first part of this paper introduces examples of radiofrequency interferences which can occur and EMI/EMC standards. Then the ANSYS EMI/ transient co-simulation flow and methodology are presented based on a real case study. Importance of correlations with measurements is highlighted, as it enables further evaluation EM mitigation techniques.