Nowadays, viruses are not only seen as causative agents of viral infectious diseases but also as valuable research materials for various biomedical purposes, including recombinant protein production. When expressed in living or cell-free expression systems, viral structural proteins self-assemble into virus-like particles (VLPs). Mimicking the native form and size of viruses and lacking the genetic material, VLPs are safe and highly immunogenic and thus can be exploited to develop antiviral vaccines. Some vaccines based on VLPs against various infectious pathogens have already been licenced for human use and are available in the commercial market, the latest of which is a VLP-based vaccine to protect against the novel Coronavirus. Despite the success and popularity of VLP subunit vaccines, many more VLPs are still in different stages of design, production, and approval. There are still many challenges that require to be addressed in the future before this surface display system can be widely used as an effective vaccine strategy in combating infectious diseases. In this review, we highlight the use of structural viral proteins to produce VLPs, emphasising their intrinsic properties, structural classification, and main expression host systems. We also compiled the recent scientific literature about VLP-based vaccines to underline the recent advances in their application as a vaccine strategy for preventing and fighting virulent human pathogens. Finally, we presented the key challenges and possible solutions for VLP-based vaccine production.