Cone snails are renowned for their deadly envenomation strategy where small neuro-active peptides called conotoxins are injected into prey and/or predators producing rapid paralysis. Increasingly sensitive proteomics techniques have revealed they can produce thousands of conotoxins along their venom duct, with different sections expressing different toxins. However, the injected venom represents only a small subset of the total venom complement. Therefore, understanding envenomation strategy requires characterisation of the injected venom in conjunction with duct venom. Here we present for the first time, the proteomic and transcriptomic characterisation of the injected venom of two worm-hunting cone snails Conus vexillum and Conus capitaneus of the Rhizoconus clade through the integration of highly sensitive LC-MS and LC-MS/MS data with RNA-Seq powered by 2nd generation sequencing on the 454 platform. Surprisingly, the injected venom was the simplest discovered thus far, being dominated by conotoxins belonging to the D-superfamily that are active on mammalian nicotinic acetylcholine receptors. We also report the presence of a peptide belonging to the con-ikot-ikot superfamily that was previously discovered in fish-hunting cone snails found to be active at the AMPA receptors. This illustrates the ability of cone snails to exquisitely target receptors that have vital physiological functions in prey to induce rapid paralysis with both nAChRs and AMPA type glutamate receptors shown to have important functions in worms. Interestingly, the injected venom peptides were predominantly expressed within the proximal sections of the venom duct along with lower levels of numerous other peptides. Thus, despite the expression of hundreds of peptides within the venom duct only a few were injected, suggesting the existence of a hitherto undescribed toxin selection mechanism(s).