A cost-effective manufacturing process yielding sufficient quantity and quality of a multigenic product is generally not an easy task to accomplish due to product complexity. Despite the success of the BEVS in producing VLP-based vaccines for both veterinary and human use, its performance regarding the expression of complex VLPs has room for improvement. The yields of correctly assembled VLPs and associated levels of baculovirus contamination are still not satisfactory according to commercial requirements. Significant efforts to address these issues continue to be directed towards ameliorating molecular design for the construction of more efficient and reliable expression systems. Nonreplicative rBVs represent one advance that aims at debottlenecking the problem of contamination of the VLP bulk with viral material. Stable protein expression through engineered insect cell lines constitutes another alternative since it does not rely on viral infection for protein production, thus minimizing downstream challenges. Still, VLP production will benefit from improvements in downstream processes that could improve recovery yields without compromising quality. Further work should also be conducted towards tuning the expression levels of each protein subunit to improve the assembly efficiency of complex VLPs and also the consistency of the final product composition. Ultimately, advances in the fields of systems biology and genetic engineering will complement each other towards the development of faster, robust and simpler production processes based on effective biological hosts and vectors. In the end, all will contribute to the sustainability of the insect cell technology and reinforce its credibility as a platform for the production of complex VLP vaccines.