Streptococcus pneumoniae (pneumococcus) is a respiratory commensal which can cause invasive pneumococcal disease (IPD). The key virulence factor of S. pneumoniae, a polysaccharide capsule encoded by the cps locus, has over 100 known serotypes. The capsule inhibits host phagocytosis and is the target of the pneumococcal conjugate vaccine (PCV). The 13-valent PCV formulation in Australia has reduced the incidence of vaccine-type IPD, however, breakthrough infections can occur due to infections by non-PCV targeted capsular serotypes or non-typable pneumococci (NTP). The NTPs includes atypical (lacking capsular genes), phenotypically unencapsulated strains, and strains with serotypes not recognised by available serological or molecular assays. Serotypes can be inferred in-silico from whole genome sequencing, based on the presence or absence of key genes.1,2 This approach can be informative when classical serological and molecular methods fail to assign a type. The affinity for the pneumococcus to undergo homologous recombination and capsular switching can mask reasons for a NTP designation, especially if only short-read sequencing is employed. Long-read sequencing can ameliorate this situation as longer reads span repetitive and problematic genomic regions. Accurate in-silico resolution of NTP strains will improve information available for public health and clinical management of this clinically significant pathogen, and could lead to refinements of serological and molecular methods in the future. This study aims to characterise non-typable invasive S. pneumoniae in New South Wales (NSW) using a hybridised approach with short- and long-read sequencing. All invasive pneumococci sterile site isolates from NSW are referred to the NSW Pneumococcal Reference Laboratory for serotyping. A representative subset of NTP-designated isolates were subjected to short- and long-read sequencing. In-silico serotype prediction was performed using open-source software and assemblies were interrogated to identify features responsible for the NTP designation. A preliminary study on multiple isolates from the same case revealed a reassortment of the cps locus based on short-read data. While there is no current impact on key epidemiological markers of transmission, public health investigations could be confounded due to the cps reassortment. By understanding the genomic dynamics of the NTP, we are value adding to the IPD public health response.