•Epigenetics, and in particular, chromatin modifiers.•Cancer metabolism.•Cancer stem cells.•Tumor cell signaling.•The immune system. During the Tenth Edition of the Annual Congress on “Anticancer Innovative Therapy” Milan, 23/24 January 2020, experts in the fields of immuno-oncology, epigenetics, tumor cell signaling, and cancer metabolism shared their latest knowledge on the roles of i epigenetics, and in particular, chromatin modifiers, ii cancer metabolism, iii cancer stem cells CSCs, iv tumor cell signaling, and iv the immune system. The novel therapeutic approaches presented included epigenetic drugs, cell cycle inhibitors combined with ICB, antibiotics and other off-label drugs, small-molecules active against CSCs, liposome-delivered miRNAs, tumor-specific CAR-T cells, and T-cell–based immunotherapy. Moreover, important evidence on possible mechanisms of resistance to these innovative therapies were also discussed, in particular with respect to resistance to ICB. Overall, this conference provided scientists and clinicians with a broad overview of future challenges and hopes to improve cancer treatment reasonably in the medium-short term.