A voltage contrast imaging defect detection system includes a voltage contrast imaging tool and a controller coupled to the voltage contrast imaging tool. The controller is configured to generate one or more voltage contrast imaging metrics for one or more structures on a sample, determine one or more target areas on the sample based on the one or more voltage contrast imaging metrics, receive a voltage contrast imaging dataset for the one or more target areas on the sample from the voltage contrast imaging tool, and detect one or more defects based on the voltage contrast imaging dataset.