Nanotechnology based combinatorial therapy has emerged as an effective strategy for cancer treatment due to its synergistic activity, suppression of multi-drug resistance and successful delivery to target site. The objective of this work was to develop and characterize tamoxifen citrate (TC) and coenzyme Q10 (CoQ10) lipid nanocarriers for oral breast cancer chemotherapy. Stearic acid (2%w/v) and poloxamer188 (3%w/v) were selected as optimal lipid matrix and surfactant for development of solid lipid nanocarriers (SLNs). Incorporation of lecithin into lipid matrix (SLN9) significantly reduced particle size to 180 nm and increased %EE of CoQ10 (45%). Nanostructured lipid carriers containing 10% Labrafac oil showed further decrease in particle size reaching only 81 nm and increased %EE up to 94% and 56% for TC and CoQ10, respectively. Lipid nanocapsules showed more prominent effect on decreasing particle size (36 nm). Lipid nanocarriers offered controlled drug release profiles. The study showed that lipid carriers significantly improved drugs permeation through rabbit intestinal mucosa and suggested them as potential delivery systems for improving the bioavailability of TC/CoQ10 therapeutic molecules. Subsequent studies will be performed in order to elucidate the cytotoxicity and genotoxicity of selected lipid nanocarriers formulas on MCF-7 (adenocarcinoma breast cancer cells) versus normal cells (WISH cell line).