The emergence and dynamic prevalence of genetic disorders and infectious diseases with mutations pose significant challenges for public health interventions. This study investigated the parameter estimation approach and the application of the dynamic state-space Markov modeling of these conditions. Using extensive simulations, the model demonstrated robust parameter estimation performance, with biases and mean-squared errors decreasing as sample size increased. Applying the model to COVID-19 data revealed distinct temporal patterns for each variant, highlighting their unique emergence, peak dominance, and decline or persistence trajectories. Despite the absence of clear trends in the data, the model exhibited a remarkable accuracy in predicting future prevalence trends for most variants, showcasing its potential for real-time monitoring and analysis. While some discrepancies were observed for specific variants, these findings suggest the model’s promise as a valuable tool for informing public health strategies. Further validation with larger datasets and exploration of incorporating additional factors hold the potential for enhancing the model’s generalizability and applicability to other evolving diseases.