Background: Pets, especially cats and dogs, represent a great potential for zoonotic transmission, leading to major health problems. The purpose of this systematic review was to present the latest developments concerning colistin resistance through mcr genes in pets. The current study also highlights the health risks of the transmission of colistin resistance between pets and humans. Methods: We conducted a systematic review on mcr-positive bacteria in pets and studies reporting their zoonotic transmission to humans. Bibliographic research queries were performed on the following databases: Google Scholar, PubMed, Scopus, Microsoft Academic, and Web of Science. Articles of interest were selected using the PRISMA guideline principles. Results: The analyzed articles from the investigated databases described the presence of mcr gene variants in pets including mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-8, mcr-9, and mcr-10. Among these articles, four studies reported potential zoonotic transmission of mcr genes between pets and humans. The epidemiological analysis revealed that dogs and cats can be colonized by mcr genes that are beginning to spread in different countries worldwide. Overall, reported articles on this subject highlight the high risk of zoonotic transmission of colistin resistance genes between pets and their owners. Conclusions: This review demonstrated the spread of mcr genes in pets and their transmission to humans, indicating the need for further measures to control this significant threat to public health. Therefore, we suggest here some strategies against this threat such as avoiding zoonotic transmission.