Fully synthetic vaccine, in which one or multi-molecular antigens are conjugated to a synthetic carrier with well-defined chemical structure, is a new direction to develop carbohydrate-based vaccine against cancer and pathogens. Toll like receptor (TLR) agonists with the ability to stimulate immune response have been widely investigated and been applied as build-in adjuvants to construct fully synthetic vaccines. In particular, remarkable progress has been achieved in recent years in the development of vaccines constructed with the agonists of TLR1/2, TLR2/6 and TLR4 and tumor-associated carbohydrate antigens (TACAs). These di-, tri- or multi-component vaccine candidates showed attractive immunological properties. This review highlights recent advances in developing full synthetic carbohydrate antigen based vaccines, with an emphasis on the structure-activity relationships that provide a primary basis for future vaccine design and immunotherapy developing.