Infections by the Rhipicephalus microplus tick represent a serious health problem in the global livestock industry, mainly due to direct damage and the vector’s capacity to transmit various pathogens. Currently, tick infections have been increasing due to the emergence of populations resistant to ixodicides. Therefore, the search for new targets that contribute to the control of this ectoparasite is a priority. At the same time, studying biological interactions between host, vector, and pathogen, including the microbiota, is a novel but little-explored field. In relation, we know that the immunoendocrine system plays a primary role in these interactions since it is responsible for regulating the health-disease process. Additionally, this macrosystem is related to various immune mechanisms for controlling pathogens and processes associated with the reproduction and development of ticks. Therefore, the study of the immunoendocrine system provides an excellent field in searching for regulatory molecules with vaccine potential or as targets for developing new drugs.