Oncolytic viruses, defined as viruses capable of lysing cancer cells, emerged as a groundbreaking class of therapeutic entities poised to revolutionize cancer treatment. Their mode of action encompasses both direct tumor cell lysis and the indirect enhancement of anti-tumor immune responses. Notably, four leading contenders in this domain, Rigvir® in Latvia, T-VEC in the United States, H101 in China and Teserpaturev (DELYTACT®) in Japan, have earned approval for treating metastatic melanoma (Rigvir and T-VEC), nasopharyngeal carcinoma and malignant glioma, respectively. Despite these notable advancements, the integration of oncolytic viruses into cancer therapy encounters several challenges. Foremost among these hurdles is the considerable variability observed in clinical responses to oncolytic virus interventions. Moreover, the adaptive immune system may inadvertently target the oncolytic viruses themselves, diverting immune resources away from tumor antigens and undermining therapeutic efficacy. Another significant limitation arises from the presence of preexisting immunity against oncolytic viruses in certain patient populations, hampering treatment outcomes. To circumvent this obstacle, researchers are investigating the utilization of animal viruses, for which humans lack preexisting immunity, as a compelling alternative to human-derived counterparts. In our comprehensive review, we delve into the intricate nuances of oncolytic virotherapy, elucidating the multifaceted mechanisms through which these viruses exert their anti-cancer effects. Furthermore, we provide a thorough examination of animal-derived oncolytic viruses, highlighting their respective strengths and limitations. Lastly, we explore the promising potential of leveraging animal viruses as potent oncolytic agents, offering new avenues for enhancing the efficacy and reach of human cancer therapeutics.