With ever-increasing data volumes, it is essential to develop automated approaches for identifying nanoscale defects in transmission electron microscopy (TEM) images. However, compared to features in conventional photographs, nanoscale defects in TEM images exhibit far greater variation due to the complex contrast mechanisms and intricate defect structures. These challenges often result in much less labeled data and higher rates of annotation errors, posing significant obstacles to improving machine learning model performance for TEM image analysis. To address these limitations, we examined transfer learning by leveraging large, pre-trained models used for natural images. We demonstrated that by using the pre-trained encoder and L2-regularization, semantically complex features are ignored in favor of simpler, more reliable cues, substantially improving the model performance. However, this improvement cannot be captured by conventional evaluation metrics such as F1-score, which can be skewed by human annotation errors treated as ground truth. Instead, we introduced novel evaluation metrics that are independent of the annotation accuracy. Using grain boundary detection in UO2 TEM images as a case study, we found that our approach led to a 57% increase in defect detection rate, which is a robust and holistic measure of model performance on the TEM dataset used in this work. Finally, we showed that model self-confidence is only achieved through transfer learning and fine-tuning of very deep layers.