Microemulsions (MEs) were designed by an innovative rational development, characterized, and used to load up to 20 mM of Tamoxifen citrate (TMX). They were made with acceptable and well-characterized excipients for all the routes of administration. Some of their properties, such as nanometric mean size and long stability shelf life, make them interesting drug delivery systems. The results obtained after the in vitro inhibition of estradiol-induced proliferation in MCF-7 breast cancer cells demonstrated a significant effect in cell growth. A decreasing of at least 90% in viable cells was shown after the incubation with MEs containing 20 mM of TMX. Besides, two compositions which loaded 10 mM of drug showed a cytotoxic effect higher than 70%. These results encourage the evaluation of alternative protocols for this drug administration, not only for estrogen receptor (ER) positive tumors, but also for ER negative.