Our data indicate that (i) an effective CD8+ T cell 3D motility is supported mainly by glucose- and glutamine-fueled TCA cycle sustaining both ATP and mtROS production from mitochondria and (ii) strategies targeting mitochondrial metabolism are effective in increasing the intratumoral infiltration of CD8+ CAR T cells to help them reach and kill tumor cells in preclinical solid tumor models. Here, CD8A is linked to neoplasm.