Poxviruses represent a large family of dsDNA viruses that can pose a significant threat to public health due to their ability to infect a broad range of hosts and spread in human populations. Vaccinia virus (VACV) has become a model to study poxvirus biology and pathogenicity. However, the diversity of this viral family remains overlooked and knowledge about other members is critically lacking. We decided to study the intricate structural details of three poxviruses using state-of-the-art cryo-electron tomography (cryoET) and advanced subvolume averaging processing. At IRBA, we developed a dedicated sample preparation workflow to be able to analyze native poxvirus samples of purified infectious particles in biological safety level 3 environment. By elucidating virion structures at high resolution and in the native environment, we aim at increasing our understanding of poxvirus diversity at the structural level to improve our preparedness and provide new targets for the future development of antiviral strategies.