Background <p>Hyaluronidase remains the mainstay treatment for impending filler-induced facial skin necrosis. Complete resolution of impending skin necrosis following hyaluronidase injection is estimated to be around 77.8%. Current practices are varied but most involve flooding 1500 international units (IU) of hyaluronidase into the suspect area. Image-guided hyaluronidase administration has shown improved outcomes with lower doses of hyaluronidase; however, no reviews have been conducted.</p> Objectives <p>To characterize and establish the proportion of patients treated successfully with ultrasound-guided hyaluronidase for impending filler-induced facial skin necrosis.</p> Methods <p>This systematic review and meta-analysis queried four international databases from inception until September 2024 for sources including two or more patients receiving ultrasound-guided hyaluronidase for impending filler-induced facial skin necrosis. Random-effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the pooled proportion of complete scar resolution after ultrasound-guided hyaluronidase. The Joanna Briggs Institute checklists were utilized to assess intra-study risk of bias, and the certainty of evidence rated using the GRADE approach.</p> Results <p>Four studies totaling 55 patients were included in the analysis. The pooled proportion of complete scar resolution after ultrasound-guided hyaluronidase is probably 94.6% (95%-CI 80.6–98.7%, 4 studies, 55 patients, <i>p</i>_egger= 0.06, moderate certainty). Two of four studies utilized image-guided hyaluronidase after failure of conventional flooding with 1500 IU. There was no statistical difference between ultrasound-guided injection of hyaluronidase intra-arterially and into hyaluronic acid deposits (<i>p </i>= 0.36).</p> Conclusion <p>Ultrasound-guided hyaluronidase represents a compelling step forward for complete resolution of impending filler-induced facial skin necrosis. Clinicians may wish to consider ultrasound-guided hyaluronidase as a first-line intervention considering the significant increase in the proportion of patients with better outcomes compared to non-image-guided intervention. More studies and higher-powered analyses are required to further confirm our findings.</p> Protocol Registration <p>CRD42024585657.</p> Level of Evidence I <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors &#xa0;<a href="http://www.springer.com/00266">www.springer.com/00266</a></p>