Nanoparticle-based therapeutics have been applied in a broad range of clinical and pre-clinical applications from diagnosis to treatment for cancer. A wide range of synthetic and naturally occurring materials such as polymers, metal oxides, silicate, liposomes, and carbon nanotubes have been developed to overcome key barriers in small molecule therapeutics including intracellular trafficking, cell/tissue targeting, poor biodistribution, and low efficiency. Virus like particles (VLPs)—engineered and non-infectious self-assembling systems based on viral nanostructures—are new approach toward overcoming these limitations, as they are a protein-based nanomaterial that closely mimics the highly symmetrical and polyvalent conformation of viruses while lacking the viral genomes. Their innate biocompatibility, biodegradability, monodispersity, mild immunogenicity, and safety combined with the capacity to chemically modify the interior and exterior surfaces of these systems offer scientists a highly customizable tool to design and engineer multi-component therapeutic agents. In this review, we discuss how these systems have been used in a wide array of cancer treatments including phototherapy, immunotherapy, gene therapy, and chemotherapy.