Plastic surgery and regenerative medicine have seen significant advancements in recent years, particularly in the realm of tissue repair, remodeling, and regeneration. One of the most promising regenerative approaches involve the use of mesenchymal stem cells and nanofat, which are novel technologies that aim to enhance the healing process of human tissues following the use, sometimes incautious and without adequate knowledge, of synthetic materials. The integration of these approaches has remarkable potential in mitigating the adverse effects caused by synthetic materials such as dermal fillers or silicone implants on the human tissues, promoting tissue homeostasis, restoration, and regeneration, and offering new avenues for clinical interventions. This comprehensive chapter explores the benefits of exploiting the use of synthetic materials in plastic, reconstructive, aesthetic surgery, and cosmetic medicine, their most common complications and how mesenchymal stem cells and nanofat can improve tissue repair of damaged tissues due to injected synthetic materials, focusing on their applications, mechanisms of action, and potential future perspectives.