Recent advances and successes in immunotherapy have resulted in its increasing use as a highly promising therapeutic strategy, based on its less toxic and durable effects. However, the success of immune checkpoint blockade therapy has been limited to immunologically “hot” tumors with high T cell infiltration. One of the potential therapeutic approaches is to activate innate immunity within the tumor microenvironment to promote T cell infiltration and enhance antitumor immune responses in “cold” tumors. This collection is looking for some novel methods to target innate immunity in cancer therapy, including therapeutic stimulation strategies of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), as well as the DNA sensing cGAS/STING pathway or any therapeutic modulation methods of innate immune cell types, such as dendritic cells (DCs), macrophages, natural killer (NK) cells, neutrophils, myeloid-derived suppressor cells (MDSCs), and Mast cells.