Process defects, either random or systematic, are often the top killers of any semiconductor device. Process defect learning and reduction are the main focuses in both technology development stage and product manufacturing yield ramp stage. In order to achieve fast defect learning, in-line defect inspection is implemented in critical layers during wafer manufacturing. In-line defect inspection is able to detect defects. However, in-line defect inspection alone cannot predict the impact of defects on device functional yield. Failure analysis is an effective method of finding the defects which really cause device functional failures. However, often, the defects found by failure analysis are very different from the original defects, making it difficult to understand the root cause. This paper will describe a methodology how to combine in-line defect inspection and failure analysis together to found the top killer defects and accelerate their root cause identification for fast defect learning and yield improvement.