The continual evolution of SARS-CoV-2 has significantly influenced the global response to the COVID-19 pandemic, with the emergence of highly transmissible and immune-evasive variants posing persistent challenges. The Omicron variant, first identified in November 2021, rapidly replaced the Delta variant, becoming the predominant strain worldwide. In Florida, Omicron was first detected in December 2021, leading to an unprecedented surge in cases that surpassed all prior waves, despite extensive vaccination efforts. This study investigates the molecular evolution and transmission dynamics of the Omicron lineages during Florida’s Omicron waves, supported by a robust dataset of over 1000 sequenced genomes. Through phylogenetic and phylodynamic analyses, we capture the rapid diversification of the Omicron lineages, identifying significant importation events, predominantly from California, Texas, and New York, and exportation to North America, Europe, and South America. Variants such as BA.1, BA.2, BA.4, and BA.5 exhibited distinct transmission patterns, with BA.2 showing the ability to reinfect individuals previously infected with BA.1. Despite the high transmissibility and immune evasion of the Omicron sub-lineages, the plateauing of cases by late 2022 suggests increasing population immunity from prior infection and vaccination. Our findings underscore the importance of continuous genomic surveillance in identifying variant introductions, mapping transmission pathways, and guiding public health interventions to mitigate current and future pandemic risks.