Highly selective and rapid sensing of adenosine (AdN) based on novel photoluminescent vanadium nanoclusters (VNCs) anchored on molybdenum disulfide nanosheets (MoS2-NS) are reported for the first time. The remarkably photoluminescent VNCs features excellent water solubility, ultra-small size, and bright photoluminescence. The VNCs on the MoS2-NS (MoS2-NS/VNCs) are well dispersed in aqueous solution and features a remarkable increase in bandgap energy (2.67 eV) compared to MoS2-NS (2.10 eV). The photoluminescence of VNCs was quenched by MoS2-NS via photoluminescence resonance energy transfer (PRET) mechanism. Furthermore, MoS2-NS/VNCs exhibit high selectivity and sensitivity toward AdN over other AdN analogues, biomolecules, and metal ions. Consequently, the absorption spectral maxima appeared at 650 nm and emission significantly enhanced in intensity at 525 nm. Interestingly, the stronger binding of AdN with MoS2-NS/VNCs was fast with nearly 65.7 % photoluminescence restored in less than 5 min. The PL lifetime of MoS2-NS/VNCs (τ1 = 8.20 ns, τ2 = 0.68 ns) increased (τ1 = 10.48 ns, τ2 = 0.79 ns) in the presence of AdN. The observed limit of detection was 29 pM. This VNCs sensor system can be constructed as XNOR logic gate with MoS2 and AdN as chemical inputs by examining the mode of emission. Finally, this probe was used to detect AdN in live cells and human serum samples with satisfactory results.