The thiophene nucleus has been established as the potential entity in heterocyclic chemistry's growing chemical world with promising pharmacological activities. Thiophene-based azo dyes compounds synthesized through different routes bear variable magnitudes of various activities such as textile, food, cosmetic, polymer, leather articles, paints, and ink industries numerous potential applications accredited to the azo function. The double bond linkage between two N atoms is widely found as a chief scaffold in a massive library of kind of organic compounds that show promising industrial and biological properties. The knowledge of various synthetic pathways and the diverse physicochemical parameters of such compounds draw the special attention of medicinal chemists to produce a combinatorial library. The present review provides a broad view of the synthesis and properties of compounds with thiophene nuclei. Therefore, it is a significant surge in designing novel azo dyes and introducing advanced synthetic routes for their preparation.