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Among all diseases, cancer has the highest fatality rate in the world. Conventional therapies have come a long way, but they still are not a panacea for cancer. Nanotechnology-based compositions of several nanoparticles (NPs) hold promise as a cancer therapy. The co-delivery of amphiphilic molecules is feasible with lipid-polymer hybrid nanoparticles (LPHNPs). Increased encapsulation of pharmaceuticals with a regulated release profile is made possible by the physical benefits of polymers and the resembling features of lipids. For increased cytotoxicity against cancer, LPHNPs have been created for the co-transport of phytochemicals and other chemotherapeutic medicines. Specifically, LPHNPs are used as carrier systems to deliver drugs to tumour locations in a regulated fashion. This method makes use of the biocompatibility of lipids and the structural advantages of polymers to provide controlled drug administration. Co-loaded LPHNPs demonstrated improved cytotoxicity, and the incorporation of phytochemicals into various medications resulted in enhanced chemo-sensitization of carcinomas. The shortcomings of existing nano-delivery systems and the benefits of LPHNPs have been discussed in this review.