Pre-flight predictions of spacecraft interactions with “complex” environments, such as the exhaust plume from plasma thrusters or the dusty environment near lunar surface, are often extremely challenging due to the complex nature of the physics, the difficulty of matching in-flight conditions in a laboratory, and a lack of flight testing opportunity. This talk presents some recent advances in understanding and predicting plasma interaction effects for spacecraft in complex environments using first-principle based and experimentally validated simulations. I will first present a new particle simulation model designed to handle the complex boundary conditions accurately while maintaining the computational speed of the standard PIC code. I will then discuss two simulation studies. The first concerns with ion thruster plume plasma interaction and contamination for the DAWN spacecraft. The second concerns with charging and charged dust particle interactions for spacecraft on lunar surface.