There are several types of breast cancer where the breast's cells proliferate uncontrollably. A selective oestrogen receptor modulator called Tamoxifen citrate (TAM) is used to treat and prevent breast cancer in both men and women. TAM is classified as class II under the biopharmaceutical categorization system (BCS) of medications. It exhibits low plasma levels, which can result in therapeutic failure due to its poor water solubility. To improve its chemotherapeutic efficiency and drug targeting, nanotechnology was exploited. In this article, TAM-loaded SLNs were prepared, characterized, and radiolabelled with Technetium-99m ([Tc]Tc) using stannous salts followed by the assessment of their radiochemical efficiency and in vivo biodistribution compared to the radiolabelled free TAM ([Tc]Tc-TAM). The results showed that the concentration of lipid had a highly prominent effect on the particle size and encapsulation efficiency of the drug, where the best selected formula showed spherical, non-aggregated morphology with a 134.6 ± 0.3 nm size and 83.9 ± 2.5% drug encapsulation. The radiolabelling purity was more than 97.4%, and it was stable for at least 6 h. In solid tumor-bearing mice, [Tc]Tc-TAM-SLNs exhibited around 3 times more uptake than [Tc]Tc-TAM solution. Accordingly, [Tc]Tc-TAM-SLNs can be suggested as a useful targeted delivery strategy for chemotherapy drugs.