Background <p>Botulinum neurotoxin (BoNT) is increasingly used for aesthetic contouring of the lower extremities, particularly for reducing calf muscle hypertrophy to achieve a slimmer leg silhouette. However, successful outcomes require precise anatomical knowledge of target muscles and their intramuscular neural distribution.</p> <p>This study aims to define optimal BoNT injection zones for key lower limb muscles based on detailed anatomical mapping, to guide safe and effective lower extremity contouring.</p> Methods <p>A total of 48 muscles—including the gastrocnemius, soleus, peroneus longus, peroneus brevis, vastus medialis, and vastus lateralis—were dissected from Korean cadavers. Intramuscular neural arborization patterns were identified using a modified Sihler’s staining technique. Each muscle was divided into standardized zones to determine ideal injection sites based on nerve distribution and bulk.</p> Results <p>For the soleus, optimal injection sites were identified in Zones 3 and 5; for the gastrocnemius, Zones 3–4 showed the highest nerve arborization. The peroneal muscles and vastus group also showed region-specific neural patterns that guided targeted injections. Recommended dosing strategies were proposed to reduce hypertrophy while preserving muscle function. Ultrasound guidance was emphasized for deep or structurally sensitive muscles.</p> Conclusions <p>Zone-based BoNT injection techniques informed by neural mapping offer a safer and more effective approach to lower extremity contouring. These anatomical insights can optimize aesthetic outcomes and minimize functional complications. Further clinical studies are needed to validate long-term efficacy and refine dosing protocols.</p> <p>Level of Evidence: Not ratable.</p>