This case report describes the successful use of Integra® (Integra LifeSciences Corporation, Plainsboro, New Jersey, United States), an artificial skin substitute, for the reconstruction of soft tissue defects following soft tissue sarcoma resection. We present a case of a 75-year-old female presented with a progressively enlarging lesion on her right hand. Imaging revealed tumor involvement in the extensor tendons and adjacent to the index finger tendon. A percutaneous biopsy confirmed an undifferentiated pleomorphic sarcoma. The patient underwent neoadjuvant radiotherapy followed by wide excision of the tumor. Integra® dermal regeneration matrix was utilized to cover the exposed bone during the surgical procedure. This allowed for wound closure and provided a favorable environment for tissue regeneration and subsequent split-thickness skin graft. Complete wound healing was obtained. Regular follow-up examinations showed no evidence of local recurrence or secondary lesions after one year. The successful use of Integra®, in this case, demonstrates its efficacy as a reconstructive option for complex hand sarcomas. It offers immediate wound coverage and promotes tissue regeneration, thereby avoiding the need for more extensive treatment modalities with associated donor-site morbidity. The utilization of Integra® resulted in high patient satisfaction and excellent recovery. This case highlights the importance of utilizing innovative techniques and materials in achieving optimal outcomes in challenging hand sarcoma reconstructions.