Solid cancers present formidable barriers against the use of adoptive cell therapies, including functional suppression of T cells and inhibition of their localization. Shown is a schematic of a nanoreagent that can—as a singular therapeutic—safely decrease the numbers of immunosuppressive cells in the tumor microenvironment and, at the same time, boost key mediators of antitumor immune responses. To propel homing to tumors, this liposomal drug carrier is decorated with an iRGD peptide. To attenuate immunosuppression in the tumor microenvironment and simultaneously increase the number and activity of tumor-specific effector immune cells, two immunomodulatory agents were chosen as nanoparticle cargo: PI-3065, a selective inhibitor of the p110δ PI3K kinase (orange), and 7DW8-5, an immunostimulant-invariant natural killer T-cell (iNKT) agonist with 100-times higher potency than its parental compound, α-GalCer (green). For details, see article by Fan Zhang and colleagues on page 3718.