Fusarium oxysporum f.sp. vasinfectum (FOV) and Verticillium dahliae occupy a special place among the pathogenic fungi that affect plant productivity, causing annually serious damage to the yield, fiber quality, morpho-biological and agronomic properties of the cotton plants. Therefore, the study of the complex molecular processes that occur between the pathogen and the plant remains one of the most important tasks. This requires molecular geneticists and breeders to fully understand the defense mechanism that has emerged in cotton plants against pathogens and to be able to apply it correctly in practice. To combat pathogenic fungi, a thorough analysis of the natural defense mechanisms of plants, including miRNA, transcription factors (TFs), quantitative trait loci (QTL), regulatory functions of plant cell membranes and proteins, may be of great importance. In this paper, we reviewed the research conducted in recent years to identify miRNAs, TFs and QTLs participating in the defense mechanism against FOV and V. dahliae. This review provides insight to understand research aimed at reducing and controlling the future economic damage caused by pathogenic fungi. Studying those factors by using modern genomic technologies together with OMICS studies has accelerated research in this discipline. As a result, the integration of various methods has emerged, developing new approaches such as multi-omics. Integrating these promising methodologies will enhance our comprehension of the molecular mechanisms underlying wilt resistance in cotton plants, leading to the development of novel resistant varieties.