Twin boundaries (TBs) have been observed in and introduced into nonmetallic materials in recent years, which brought new concepts for the design of new structural materials. However, the roles of TB on the mechanical properties and strengthening/softening of transition metal nitrides remain unclear. To investigate the TB effects and the in-plane anisotropy, nanoindentations on VN (111) films with and without TB were simulated with molecular dynamics, in which a cylindrical indenter was used, and its longitudinal axis were assigned along <112> and <110>, respectively. We found that the effect of the indenter orientation is insignificant in the elastic stage, but significant in the following inelastic deformation. Different deformation mechanisms can be found for inelastic deformation, such as twinning and dislocation glide. The migration of TB can be observed, which may release the internal stress, resulting in softening; while the dislocation locking and pileup at TB can enhance the strength. We also found that the strengthening/softening induced by TB depends on the deformation mechanisms induced by indenter directions.