Nonpharmaceutical and pharmaceutical public health interventions are important to mitigate the coronavirus disease 2019 (COVID-19) epidemic. However, it is still unclear how the effectiveness of these interventions changes with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel variants. This simulation study utilized data from Japan and investigated how the characteristic properties of the Omicron variant, which emerged in late 2021, influence the effectiveness of public health interventions, including vaccination, the reduction of interpersonal contact, and the early isolation of infectious people. Although the short generation time of the Omicron variant increases the effectiveness of vaccination and the reduction of interpersonal contact, it decreases the effectiveness of early isolation. The latter feature may make the containment of case clusters difficult. The increase of infected children during the Omicron-dominant epidemic diminishes the effects of previously adult-targeted interventions. These findings underscore the importance of monitoring viral evolution and consequent changes in epidemiological characteristics. An assessment and adaptation of public health measures against COVID-19 are required as SARS-CoV-2 novel variants continue to emerge.