Adoptive cell therapy (ACT) has emerged as a promising approach for the treatment of various cancers. The therapeutic regime of ACT involves the isolation and expansion of tumor-specific αβ T cells from cancer patients and the reinjection of these T cells into patients or the genetic modification of T-cell receptors (TCRs) to generate chimeric antigen receptor (CAR) T cells, which are subsequently used for ACT. In comparison, conventional ACT relies primarily on αβ T cells, recent research has expanded the scope of adoptive cellular therapies to include unconventional T-cell subsets, such as γδ T cells and invariant natural killer T (iNKT) cells or mucosal-associated invariant T (MAIT) cells. These unique T-cell populations offer distinct immunological properties and hold great promise for innovative approaches in cancer immunotherapy. γδ T cells, iNKT, and MAIT cells can recognize some unique antigen signatures on cancer cells and show greater flexibility and specificity in preferentially targeting malignant cells in the body. In this chapter, we discuss several approaches to harness the antitumor properties of unconventional T lymphocytes, such as their isolation, expansion, and genetic engineering techniques, to improve their efficacy in cancer therapeutics. We further provide insights into the opportunities and challenges of using these unconventional ACTs in recent advancements in cellular therapies to target cancer.