Nanopattern replication of complex structures by plastic injection is a challenge that requires simulations to define the right processing parameters. Previous work managed to simulate replication for single cavities in 2D and 3D, showing high performance requirements of CPU to simulate periodic trenches in 2D. This paper presents two ways to approach the simulation of replication of complex 3D hydrophobic surfaces. The first approach is based on previous CFD Ansys Fluent and compared to FE based CFD Polyflow software for the analysis of laminar flows typical in polymer processing and glass forming as well as other applications. The results showed that Polyflow was able to reduce computing time from 72 h to only 5 min as desired in the project. Furthermore, simulations carried out with Polyflow showed that higher injection and mold temperature lead to better replication of hydrophobicity in agreement with the experiments. Polyflow simulations are proved to be a good tool to define process parameters such as temperature and cycle times for nanopattern replication.