As the latest identified novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant of concern (VOC), the influence of Omicron on our globe grows promptly. Compared with the last VOC (Delta variant), more mutations were identified, which may address the characteristics of Omicron. Considering these crucial mutations and their implications including an increase in transmissibility, COVID‐19 severity, and reduction of efficacy of currently available diagnostics, vaccines, and therapeutics, Omicron has been classified as one of the VOC. Notably, 15 of these mutations reside in the receptor‐binding domain of spike glycoprotein, which may alter transmissibility, infectivity, neutralizing antibody escape, and vaccine breakthrough cases of COVID‐19. Therefore, our present study characterizes the mutational hotspots of the Omicron variant in comparison with the Delta variant of SARS‐CoV‐2. Furthermore, detailed information was analyzed to characterize the global perspective of Omicron, including transmission dynamic, effect on testing, and immunity, which shall promote the progress of the clinical application and basic research. Collectively, our data suggest that due to continuous variation in the spike glycoprotein sequences, the use of coronavirus‐specific attachment inhibitors may not be the current choice of therapy for emerging SARS‐CoV‐2 VOCs. Hence, we need to proceed with a sense of urgency in this matter. Highlights First report of characterization of the novel SARS‐CoV‐2 Omicron (B.1.1.529) Variant of Concern (VOC). Omicron variant is the most divergent SARS‐CoV‐2 variant characterized as the highest number of amino acid substitutions identified in spike glycoprotein, till date. These mutations in Omicron may be linked with more transmissibility, robust viral binding affinity, and immune escape. Coronavirus specific attachment inhibitors may not be the current choice of therapy for SARS‐CoV‐2 Omicron (B.1.1.529).