The main difference between a seamless bra and a bralette is the level of support they provide. Seamless bras are designed to be more supportive and structured, with features like underwire and molded cups. Bralettes, on the other hand, are designed to be more lightweight and comfortable, with little to no support features. Additionally, bralettes are often designed to be worn as a fashion statement, while seamless bras are designed to be worn as an everyday bra.