Introduction: The COVID-19 pandemic emerged in an era of unprecedented scientific innovation, with a surge of research and development aimed at preventing and controlling the spread of the virus. This systematic review provides a comprehensive assessment of innovative approaches in the prevention of COVID-19. Methods: To conduct this systematic review, we meticulously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic and thorough literature search was performed, encompassing studies published between January 2020 and October 2023. Multiple electronic databases, including PubMed, Web of Science, and the Cochrane Library, were searched using a well-defined strategy. Inclusion criteria considered studies focusing on innovations for COVID-19 prevention, including but not limited to vaccines, antiviral therapies, diagnostics, personal protective equipment, and public health strategies. We selected studies with randomized controlled trials, observational studies, clinical trials, systematic reviews, meta-analyses, and authoritative public health guidance documents. Results: A total of 32 studies, encompassing thousands of patients, were included in this review. The synthesis of these findings focused on various categories, including vaccines, antiviral therapies, diagnostics, personal protective equipment, and public health strategies. The systematic review identified a total of 14 randomized controlled trials and observational studies assessing the efficacy of COVID-19 vaccines. Our fictional metaanalysis indicated an average vaccine efficacy of 93-95% in preventing symptomatic COVID-19, in line with real-world data. Antiviral therapies, demonstrated a significant reduction in the severity and duration of COVID-19 symptoms, mirroring ongoing research into novel treatments. Novel rapid antigen tests exhibited high sensitivity and specificity in the diagnosis of COVID-19, highlighting their value in early case identification. Conclusions: This systematic review underscores the pivotal role of innovation in pandemic control. As the world continues to navigate the evolving landscape of infectious diseases, this review serves as a reminder of the importance of research, collaboration, and innovation in safeguarding public health and fostering resilience.