Abstract Despite tremendous efforts by the research community during the COVID-19 pandemic, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. Being a key structural component of the SARS-CoV-2 virion, the envelope encapsulates viral RNA and is composed of three structural proteins, spike (S), membrane (M), and envelope (E), which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multiscale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns formed by M’s transmembrane and intravirion (endo) domains. These results are in good agreement with current experimental data, demonstrating a generic and versatile integrative approach to model the structure of a virus de novo . We anticipate our work to provide insights into critical roles of structural proteins in the viral assembly and integration, proposing new targets for the antiviral therapies.