Ticks are the ectoparasites that cause the most damage to the veterinary industry. Because of their hematophagous habits, ticks consume significant amounts of blood, causing debilitating and immunosuppressive effects. In addition, ticks are the major transmitters of pathogens, including viruses, bacteria, and protozoa. Tick infestations are controlled with acaricides; However, the disadvantages of using them, including the increasing resistance of ticks to ixodicides, the negative impact on human and animal health and the ecological damage to the environment, force the use of sustainable alternatives such as immune control through vaccination. Although commercial vaccines against the most important cattle tick, Rhipicephalus microplus have been developed, vaccines against other tick species do not exist. In addition, vaccines based on other antigens besides Bm86, an antigen from the surface of tick midgut, have not been developed. This chapter will delve into the vital aspects of the immune response essential for tick antigens, presenting significant findings on vaccine targets, strategies, and innovations. Moreover, this chapter will examine cutting-edge approaches for vaccine development, including the emerging concept of “multi-epitopic” vaccines and vaccines derived from tick microbiota.