Two protein-based vaccines (Bexsero® and Trumenba®) are licensed for invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B (MenB). The aim of this study was to evaluate the possible protection of these vaccines, based on the genomic profiles of IMD isolates. All invasive meningococcal isolates in Sweden during 2014–2018 (n = 242) were analyzed with the vaccine coverage scheme available at the PubMLST database. The overall estimated genomic strain coverage among the Swedish invasive meningococcal isolates was 55% for Bexsero and 57% for Trumenba (p = 0.714). The estimated serogroup-specific coverage for Bexsero respectively Trumenba was: MenB; 67% and 90% (p < 0.05), MenW; 93% and 4% (p < 0.05), MenC; 87% and 30% (p < 0.05) and MenY; 1% and 96% (p < 0.05). With the combination of the two vaccines, the potential genomic-based strain coverage was 95%, indicating a possible additive effect of combining Bexsero and Trumenba, which, however, needs to be confirmed by analysis of phenotypic antigen expression.