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Ivermectin (IVM) is a drug widely used in veterinary and human medicine for the management of parasitic diseases. Its repositioning potential has been recently considered for the treatment of different diseases, such as cancer and viral infections. However, IVM faces some limitations to its formulations due to its low water solubility and bioavailability, along with reports of drug resistance. In this sense, novel technological approaches have been explored to optimize its formulations and/or to develop innovative medicines. Therefore, this review discusses the strategies proposed in the last decade to improve the safety and efficacy of IVM and to explore its novel therapeutic applications. Among these technologies, the use of micro/nano-drug delivery systems is the most used approach, followed by long-acting formulations. In general, the development of these novel formulations seems to run side by side in veterinary and human health, showing a shared interface between the two areas. Although the technologies proposed indicate a promising future in the development of innovative dosage forms containing IVM, its safety and therapeutic targets must be further evaluated. Overall, these approaches comprise tailoring drug delivery profiles, decreasing the risks of developing drug resistance, and supporting the application of IVM for reaching different therapeutic targets.