We synthesized and evaluated a novel class of chelator-free [⁶⁴Cu]CuS nanoparticles (NPs) suitable both for PET imaging and as photothermal coupling agents for photothermal ablation. These [⁶⁴Cu]CuS NPs are simple to make, possess excellent stability, and allow robust noninvasive micro-PET imaging. Furthermore, the CuS NPs display strong absorption in the near-infrared (NIR) region (peak at 930 nm); passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells occurs upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (∼11 nm), strong NIR absorption, and integration of ⁶⁴Cu as a structural component makes these [⁶⁴Cu]CuS NPs ideally suited for multifunctional molecular imaging and therapy.