Background: Soft tissue defects of the lower limbs pose significant challenges in reconstructive surgery, accounting for approximately 10% of all reconstructive free flaps performed. These reconstructions often encounter higher complication rates due to various factors such as inflammation, infection, impaired blood flow, and nerve injuries. Methods: A systematic review was conducted following PRISMA guidelines, reviewing literature from 2017 to 2024. Eligible studies included those on free flap reconstruction of lower limb defects in living human subjects, with more than three cases and reported rates of flap failure and return to the operating room. Systematic reviews and metanalysis were excluded. Results: A total of 17 studies comprising 5061 patients and 5133 free flap reconstructions were included. The most common defects were in the lower leg (52.19%) due to trauma (79.40%). The total flap necrosis rate was 7.78%, the partial necrosis rate was 9.15%, and the rate of return to the operating room for suspected vascular compromise was 13.79%. Discussion: Lower limb reconstruction presents challenges due to diverse etiologies and variable tissue requirements. Factors such as recipient vessel availability, flap selection, and multidisciplinary approaches influence outcomes. Muscle and fasciocutaneous flaps remain common choices, each with advantages and limitations. This systematic review underscores the importance of individualized treatment planning. Conclusions: Microsurgical reconstruction of lower limb defects demonstrates safety and reliability, with overall favorable outcomes. Flap selection should be tailored to specific patient needs and defect characteristics, emphasizing meticulous surgical techniques and multidisciplinary collaboration. This systematic review provides valuable insights into current standards and encourages adherence to best practices in lower limb reconstruction.