A global increase in the incidence of invasive group A streptococcal (iGAS) infections was observed after lifting COVID-19-related restrictions in 2022 with dominance of M1UK in many countries. After seasonal declines in iGAS incidence during the summer of 2023, rapid expansion of a previously rare emm type 3.93 was observed the Netherlands from November 2023, causing 60% of all iGAS cases within 4 months. To determine the molecular signatures underpinning these trends, we conducted a genome wide association study on 557 pre-COVID carriage and iGAS isolates compared to 411 post-COVID isolates, as well as a phylogenetic analysis on 111 pre-COVID and recent emm3.93 isolates, of which 20 were assembled into closed genomes. Preliminary results highlight that the presence of insertion sequences/transposase genes and prophages, which often contain virulence factors, are associated with the invasive capability of GAS. Additionally, we discovered the emergence of three new emm3.93 clades with a ~200 kb prophage-mediated genome inversion around the terminus that may confer bacterial advantages. Specialised streptococcal proteomics analysis on genetically closely-related emm3.93 strains with and without this genomic rearrangement revealed increased expression of surface-expressed and secreted virulence factors including SpyCep, C5A peptidase, streptokinase, streptolysin S and superantigen SpeA. Together, our findings suggest that strains with the ability to significantly alter their expression profiles via large genomic alterations may best adapt to and overcome host defences when causing invasive disease. Our findings also underscore the value of molecular surveillance, especially combined short and long read sequencing, in identifying clinical and public health threats.