The emergence of cellular immunotherapy has revolutionized cancer treatment. Amidst the arsenal of immune cells, tumor-infiltrating lymphocytes (TILs) have emerged as potent warriors in the battle against cancer. From the initial recognition of tumor antigens to the complex orchestration of immune responses, the story of TILs unfolds as a promising narrative in the ever-evolving landscape of cancer therapy. This chapter explores the evolving landscape of TIL-based cancer therapy, encompassing their role in the immune microenvironment and nuanced interplay between TILs and cancer. This chapter also explores the methods of isolation of TILs, ex vivo expansion, and the transformative outcomes observed in clinical applications. Delving into the molecular intricacies of TIL–cancer interactions, we have discussed the potential and challenges inherent in harnessing TILs for the personalized treatment of diverse malignancies.