The emergence of the XBB.1.16 Omicron subvariant of COVID-19 has been a cause for concern for the WHO and health authorities globally. This subvariant, which originated from a hybrid of two BA.2 progeny pedigree, has two amino acid mutations in its spike protein and shares a genetic makeup similar to the XBB.1.5 variant. The WHO initially labeled it as a variant under monitoring before elevating it to a variant of interest after it was found to have caused a surge of COVID-19 cases in India for seven months. The XBB.1.16 subvariant has a proliferative edge and can evade the immune system. It has been spreading rapidly on a global scale and has been linked with a higher effective reproductive number than other subvariants. As such, a concerted international effort to prevent and contain its transmission has been recommended. Health authorities must strengthen their health systems, surveillance, and data collection systems to enable them to detect, track, and respond to emerging and reemerging strains of the virus in a timely and effective manner. Research into the XBB.1.16 subvariant is crucial for alerting and preparing the global populace for a potential outbreak, developing treatment options, and potential vaccines. Implementing the One Health approach can promote greater collaboration between diverse disciplines and societal levels to build a more resilient and sustainable future for all.