To facilitate the field of biomedical engineering, rapid DNA sequencing utilising two-dimensional materials (2D) holds enormous significance. Here, the interaction of the 2D-Cobalt Telluride (2D-CoTe2) with all four mono-nucleobase single-stranded DNAs (ssDNAs) has been studied using Raman spectroscopy. The Raman spectra illustrate that the guanine and the adenine bases have interacted strongly, though thymine and cytosine do not show strong interaction. These findings are further corroborated by FTIR spectroscopy, which exhibits complementary vibrational signatures corresponding to the molecular interactions. We use atomistic Molecular Dynamics (MD) simulations to study the interactions of the 2D-CoTe2 and ssDNAs at the atomic level. Binding energy calculation using the Molecular Mechanics/Generalized Born Surface Area (MMGBSA) method confirmed the interaction of the 2D-CoTe2 and ssDNA and the interaction strength follows the trend: poly-G-DNA ~ poly-A-DNA > poly-T-DNA > poly-C-DNA. Atomic force microscopic images of the mixture of 2D-CoTe2 with all four ssDNAs have been obtained, to reassure these interactions topographically, aligning with the observed trend. Finally, Raman spectroscopic analysis successfully differentiates adenine and guanine nucleotides within hybrid DNA sequences, demonstrating the potential of 2D-CoTe2 for nucleotide identification.