A recent re-emergence and outbreak of Mpox brought poxviruses back as a public health threat, underlining an important knowledge gap at their core. Now, a team of researchers from the Institute of Science and Technology Austria (ISTA) lifted the mysteries of poxviral core architecture by combining various cryo-electron microscopy techniques with molecular modeling. The findings, published in Nature Structural & Molecular Biology, could facilitate future research on therapeutics targeting the poxvirus core.