Invariant natural killer cells (iNKT) possess potent anti-tumour properties when activated with glycolipid ligands, such as alpha-galactosylceramide (aGalCer/KRN7000). Activation of iNKT cells induces a vast array of immunomodulating cytokines and transactivation of innate and tumour-specific adaptive immune cells. This event is strongly associated with the activities of CD8α⁺ dendritic cells (DCs). Previous observations using targeted nanoemulsions (TNE) to deliver OVA antigen to CD8α⁺ DCs via Clec9a (Clec9a/OVA) have demonstrated a self-adjuvanting effect on DC maturation and the efficient cross-priming of antigen-specific CD8 T cells. In this study, we have further demonstrated the intricate role iNKT cells play in the maturation of CD8α⁺ DCs and the enhancement in cross-priming of antigen-specific T cells in mice given Clec9a/OVA TNE. Comparing wild-type and NKT cell-deficient Jα18^-/- mice, we found that iNKT cells were required for the ability of Clec9a/OVA TNE treatment to activate natural killer (NK) cells. Ultimately, we showed that iNKT cells are required for enhanced induction of antigen-specific CD8 T cells by TNE. To better harness the immune potentiating effects of iNKT cells with this treatment approach, we incorporated αGalCer adjuvant into Clec9a/OVA nanoemulsions (Clec9a/OVA/aGC). Single administration of these nanoparticles was found to be tolerable in mice and could enhance the overall magnitude of immune response. Rapid maturation of CD8α⁺ DCs, increased activation of iNKT and NK cells, greater IFNγ production as well as enhanced expansion of antigen-specific CD8⁺ T cells were all observed after Clec9a/OVA/aGC treatment. When tested against an aggressive model of B cell lymphoma (Eµmyc-OVA), a single dose of Clec9a/OVA/aGC could control tumour progression in a proportion of tumour-bearing mice. Our results suggest that suppression of tumour growth requires innate immune activation and a certain threshold of systemic IFNγ production. Further investigations are ongoing to explore therapeutic efficacy against other cancers.