The development of multifunctional metal-organic frameworks (MOFs) is a desirable method to use in different applications. As a new 3D MOF decorated with thiophene-urea functions, TMU-57 (formulated as [Zn(TDC)(DPU)].0.85DMF where H2TDC = thiophene-2,5-dicarboxylic acid, DPU = 1,3-di(pyridin-4-yl)urea), has been synthesized to improve the host-guest chemistry of the material. Since, TMU-57 is decorated with electron-rich thiophene and urea functions, it can interact through hydrogen bonding and Lewis acid-base interactions with different guests. In line with this approach, it is realized that TMU-57 is one of the most sensitive sensors to phenolic nitroaromatics (NACs), particularly 2,4,6-trinitrophenol, which reaches 92.5% (9) quenching at 5 ppb with Ksv value equal to 2 (1) × 10+8 M−1 and the detection limit of 9 × 10 −9 M (k = 3, σ = 0.6). Additionally, TMU-57 shows a high capacity for Hg(II) ions equal to 570 (14) mg.g−1. This work clearly shows that the multifunctionalization strategy can extend the application of functional MOFs as an efficient host from one to multiple applications.