Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important food, feed, industrial raw materials, and new energy crops, and is widely cultivated around the world. China is the largest sweet potato producer in the world, and the sweet potato industry plays an important role in China’s agriculture. During the growth of sweet potato, it is often affected by biotic stresses, such as fungi, nematodes, insects, viruses, and bacteria. These stressors are widespread worldwide and have severely restricted the production of sweet potato. In recent years, with the rapid development and maturity of biotechnology, an increasing number of stress-related genes have been introduced into sweet potato, which improves its quality and resistance of sweet potato. This paper summarizes the discovery of biological stress-related genes in sweet potato and the related mechanisms of stress resistance from the perspectives of genomics analysis, transcriptomics analysis, genetic engineering, and physiological and biochemical indicators. The mechanisms of stress resistance provide a reference for analyzing the molecular breeding of disease resistance mechanisms and biotic stress resistance in sweet potato.