Therapeutic　metallodrugs　have　gained　substantial　success　in　cancer　treatment　and　also　motivate　the　active　exploration　of　metallodrugs　for　cancer　theranostics.　However,　it　remains　a　challenge　to　engineer　metallodrugs　with　desired　therapy　efficacy　and　safety　because　of　their　frequent　in　vivo　limited　bioavailability　and　off-target　delivery.　Herein,　an　efficient　strategy　to　design　vanadium　nanodrugs　(VNDs)　with　cancer-specific　theranostic　capability　for　visualizing/treating　in　vivo　mice　tumors,　is　developed.　The　VNDs　are　controllably　constructed　via　a　non-covalent　coordination　triggered　self-assembly　strategy,　which　allows　the　general　synthesis　of　diverse　nanoscale　metallodrugs.　Significantly,　the　VNDs　exert　an　approximately　tenfold　enhancement　of　therapy　efficacy　in　comparison　with　vanadium　compounds　and　the　clinically　used　cisplatin　due　to　their　improved　bioavailability　and　multiple　pathways-mediated　tumor-selective　therapy.　Moreover,　the　VNDs　feature　intense　near-infrared　(NIR)　absorption　and　undergo　specific　disassembly　in　the　tumor　microenvironment,　thus　enabling　tumor-specific　molecular　imaging　by　the　turn-on　NIR　fluorescence　of　embedded　labels　upon　disassembly.　Hence,　the　vanadium　nanoprodrugs　propose　a　new　paradigm　for　in　vivo　tumor-selective　therapy　and　imaging　and　may　propel　the　design　of　effective　anticancer　metallodrugs.　©　2021　Wiley-VCH　GmbH