Despite the progress made in oncological theranostics, cancer remains a global health problem and a leading cause of death worldwide. Multidrug and radiation therapy resistance is an important challenge in cancer treatment. To overcome this great concern in clinical practice, conventional therapies are more and more used in combination with modern approaches to improve the quality of patients’ lives. In this review, we emphasize how small biological entities, such as viruses, bacteria, archaea, fungi, protozoans, and microalgae, as well as their related structural compounds and toxins/metabolites/bioactive molecules, can prevent and suppress cancer or regulate malignant initiation, progression, metastasis, and responses to different therapies. All these small biological fighters are free-living or parasitic in nature and, furthermore, viruses, bacteria, archaea, fungi, and protozoans are components of human and animal microbiomes. Recently, polymorphic microbiomes have been recognized as a new emerging hallmark of cancer. Fortunately, there is no limit to the development of novel approaches in cancer biomedicine. Thus, viral vector-based cancer therapies based on genetically engineered viruses, bacteriotherapy, mycotherapy based on anti-cancer fungal bioactive compounds, use of protozoan parasite-derived proteins, nanoarchaeosomes, and microalgae-based microrobots have been more and more used in oncology, promoting biomimetic approaches and biology-inspired strategies to maximize cancer diagnostic and therapy efficiency, leading to an improved patients’ quality of life.