High flow nasal cannula (HFNC) therapy has emerged as a promising intervention in the management of acute respiratory failure (ARF). This systematic review and meta-analysis aim to evaluate the impact of HFNC therapy on oxygenation and respiratory mechanics in patients with ARF. A comprehensive search was conducted across multiple databases to identify relevant studies published up to January 2024. Studies meeting the inclusion criteria were assessed for methodological quality and relevant data were extracted for analysis. Meta-analysis was performed to quantify the effect of HFNC therapy on oxygenation parameters and respiratory mechanics. The findings suggest that HFNC therapy significantly improves oxygenation and respiratory mechanics in patients with ARF. However, further well-designed randomized controlled trials are warranted to elucidate the optimal use of HFNC therapy in this patient population.