Ablation has had a long-standing ability to kill cancer cells, but clinical methods to date have lacked intrinsic tumor specificity to energy deposition, leading to off-target heating, patient morbidity, and limited applicability. In this study, von Maltzahn and colleagues harness the unique electromagnetic properties of plasmonic gold nanorods (NR; shown in gold) as Injectable antennas that intravenously home to tumors by leaking out through fenestrated angiogenic tumor vasculature (shown in beige) and locally transduce otherwise benign nearinfrared energy into heat for tumor-specific ablation (heat depicted in red). The authors describe an integrated approach to improved plasmonic therapy, comprised of nanomaterial optimization and computational irradiation protocol development. The authors synthesized polyethylene-glycol (PEG)-protected gold NRs that exhibit superior circulation half-life in vivo (t1/2, ∼17 hours) and photothermal heat generation per gram of gold compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as ∼2-fold higher x-ray absorption than a clinical iodine contrast agent. Following intratumoral or intravenous administration, PEG-NR biodistribution data, derived via noninvasive x-ray computed tomography or ex vivo spectrometry, respectively, is fused with 4D computational heat transport modeling to predict photothermal heating during irradiation. In computationallydriven pilot therapeutic studies, it is shown that a single intravenous injection of PEGnanorods targeted human xenograft tumors in mice and enabled their complete destruction using otherwise benign near-infrared light. These studies highlight the potential for integrated computational therapy design and nanotherapeutic development to enable ultraselective tumor ablation. In the future, these materials could enable highly precise clinical tumor ablation, intraoperative margin ablation, and localized tumor hyperthermia for amplifying the efficacy of mainstay radiation and chemotherapies. For details, see the article by von Maltzahn and colleagues on page 3892 of this issue.