Checkpoint blockade immunotherapies have demonstrated remarkable therapeutic success by overcoming tumor-induced T cell inhibition, however their efficacy is poor when patients lack evidence of a spontaneous T cell response. Tumors in mice which generate a spontaneous T cell response activate the innate immune system through the STING pathway. STING agonists promote dendritic cell (DC) activation as well as subsequent priming and recruitment of T cells, leading to significant tumor control in transplantable models. However, preliminary clinical trial results suggest that STING agonists have clinical activity in only a minority of patients and have limited efficacy in non-inflamed tumors. This observation suggests a need to more closely study the non-inflamed tumor microenvironment and understand which innate immune cells and signaling pathways are required for driving tumor-specific T cell priming and recruitment in this context. Given that pathogen encounter rarely activates a single innate immune pathway, we began by investigating different TLR pathways for their potential to augment innate immune activation induced by STING. We found that the TLR4 agonist LPS was able to synergize with the STING agonist DMXAA to induce IFN-B production in vitro and was able to improve tumor control in vivo. We next addressed the possibility that STING agonists could fail due to insufficient numbers of essential DCs present in the tumor microenvironment. We found that intratumoral Flt3L promoted accumulation of CD103+ DCs and led to tumor control in combination with DMXAA and anti-PD-L1 + anti-CTLA-4 in our non-T cell-inflamed genetic mouse melanoma model. Lastly, we investigated gene expression profiles of Wilms tumors, a severely non-T cell-inflamed cancer type. We identified upregulation of DNA repair gene expression in these tumors as well as various adult tumor types including melanoma, suggesting a previously undescribed mechanism of immune evasion.