Adoptive T cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising personalized immunotherapy approach, spearheaded by Dr. Steven Rosenberg, targeting various cancer types. Despite initial challenges in TIL production, recent advancements have showcased its superiority to immune checkpoint blockade in metastatic melanoma, even after anti-PD-1 therapy failure. The expedited manufacturing process, now around 3 weeks, coupled with the US Food and Drug Administration approval of lifileucel in 2024, is poised to propel TIL therapy into mainstream oncology. This commentary delves into the critical surgical aspects of TIL harvesting, emphasizing the integral role of surgeons in ensuring optimal TIL quality, safety, and therapeutic effectiveness. By shedding light on these considerations, this article aims to guide and enhance collaborative efforts in advancing TIL therapy for patients facing limited treatment options.