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Background: SARS‐CoV‐2 genomic surveillance is necessary for the detection, monitoring, and evaluation of virus variants, which can have increased transmissibility, disease severity, or other adverse effects. We sequenced 330 SARS‐CoV‐2 genomes during the sixth wave of the COVID pandemic in Iran and compared them with five previous waves, for identifying SARS‐CoV‐2 variants, the genomic behavior of the virus, and understanding its characteristics. Methods: After viral RNA extraction from clinical samples collected during the COVID‐19 pandemic, next generation sequencing was performed using the Nextseq and Nanopore platforms. The sequencing data were analyzed and compared with reference sequences. Results: In Iran during the first wave, V and L clades were detected. The second wave was recognized by G, GH, and GR clades. Circulating clades during the third wave were GH and GR. In the fourth wave, GRY (alpha variant), GK (delta variant), and one GH clade (beta variant) were detected. All viruses in the fifth wave were in GK clade (delta variant). In the sixth wave, Omicron variant (GRA clade) was circulating. Conclusions: Genome sequencing, a key strategy in genomic surveillance systems, helps to detect and monitor the prevalence of SARS‐CoV‐2 variants, monitor the viral evolution of SARS‐CoV‐2, identify new variants for disease prevention, control, and treatment, and also provide information for and conduct public health measures in this area. With this system, Iran could be ready for surveillance of other respiratory virus diseases besides influenza and SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]