There are several mechanisms by which cancer cells develop resistance to treatments, including increasing anti-apoptosis, increasing drug efflux, inducing angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs are hard to reach curative effects due to these resistance mechanisms. It has been suggested that liposomes based co-delivery systems, which can deliver drugs and genes to the same tumor cells and exhibit synergistic anti-cancer effects, could be used to overcome the resistance of cancer cells. As the co-delivery systems could simultaneously block two or more pathways, this might promote the death of cancer cells by sensitizing cells to death stimuli. This article provides a brief review on the liposomes based co-delivery systems to overcome cancer resistance by the synergistic effects of drugs and genes. Particularly, the synergistic effects of combinatorial anticancer drugs and genes in various cancer models employing multifunctional liposomes based co-delivery systems have been discussed. This review also gives new insights into the challenges of liposomes based co-delivery systems in the field of cancer therapy, by which we hope to provide some suggestions on the development of liposomes based co-delivery systems.