As the fifth variant of concern of the SARS‐CoV‐2 virus, the Omicron variant (B.1.1.529) has quickly become the dominant type among the previous circulating variants worldwide. During the Omicron wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two Omicron subvariants, BQ.1 and XBB lineages, including BQ.1.1, XBB.1, and XBB.1.5, have become a global public health issue given their ability to escape from therapeutic monoclonal antibodies and herd immunity induced by prior coronavirus disease 2019 (COVID‐19) vaccines, boosters, and infection. In this respect, XBB.1.5, which has been established to harbor a rare mutation F486P, demonstrates superior transmissibility and immune escape ability compared to other subvariants and has emerged as the dominant strain in several countries. This review provides a comprehensive overview of the epidemiological features, spike mutations, and immune evasion of BQ.1 and XBB lineages. We expounded on the mechanisms underlying mutations and immune escape from neutralizing antibodies from vaccinated or convalescent COVID‐19 individuals and therapeutic monoclonal antibodies (mAbs) and proposed strategies for prevention against BQ.1 and XBB sublineages. In the Omicron wave, two emerging subvariants, BQ.1 and XBB, have rapidly become a global public health concern. This diagram illustrates the critical spike mutations in these subvariants, which can lead to immune escape from prior COVID‐19 vaccines, boosters, and therapeutic monoclonal antibodies (mAbs). Notably, XBB.1.5, which carries a rare F486P mutation, has demonstrated significantly higher receptor‐binding domain (RBD)‐ACE2 binding affinity and transmissibility compared to other subvariants, making it the dominant strain in several countries.