Background <p>Precise knowledge of the anatomical course of the superior and inferior labial arteries is essential for ensuring the safety of surgical interventions and minimally invasive esthetic procedures involving the lips. However, despite their growing clinical importance, the available anatomical evidence remains heterogeneous and fragmented, which limits the development of consistent safety guidelines.</p> Objective <p>To evaluate the anatomical distribution of the superior and inferior labial arteries in relation to the orbicularis oris muscle by integrating findings from a Brazilian cadaveric anatomical investigation with evidence synthesized through a systematic review and meta-analysis.</p> Methods <p>The cadaveric component was performed using preserved Brazilian specimens and standardized anatomical landmarks, dividing the lips into midline and paramedian regions located 1 cm lateral to the midline. The position of the superior and inferior labial arteries relative to the orbicularis oris muscle was classified as submucosal, intramuscular, or subcutaneous. In parallel, a systematic review and meta-analysis were conducted according to PRISMA guidelines, with electronic databases searched without date restrictions for studies reporting the anatomical location of the labial arteries. Eligible studies were quantitatively synthesized using fixed- or random-effects models depending on the degree of heterogeneity.</p> Results <p>Four studies met the eligibility criteria for quantitative synthesis. The pooled analysis demonstrated that the superior labial artery in the upper lip was most frequently located in the submucosal plane (33.3–53.3%), followed by an intramuscular course (40.0–46.7%), whereas a subcutaneous position was uncommon (0.0–26.7%). In the lower lip, the inferior labial artery showed greater variability, with intramuscular positioning predominating in median regions (73.3%) and submucosal positioning ranging from 13.3 to 53.3%, while subcutaneous localization remained rare. Regional and sex-related differences contributed to moderate-to-high heterogeneity across the analyses. The cadaveric findings were consistent with the meta-analytic results, confirming the predominance of submucosal and intramuscular arterial courses, a consistent midline anastomosis, and increased positional variability in paramedian regions.</p> Conclusions <p>The superior and inferior labial arteries demonstrate variable anatomical distribution patterns, most commonly occupying submucosal and intramuscular planes, while subcutaneous courses are uncommon. By integrating a Brazilian cadaveric study with systematic review and meta-analysis, this investigation provides comprehensive anatomical evidence with direct clinical implications for improving the safety of lip surgery and minimally invasive esthetic procedures, emphasizing that neither midline nor paramedian regions can be considered entirely risk-free.</p> No Level Assigned <p>This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="https://link.springer.com/journal/00266">https://link.springer.com/journal/00266</a>.</p>