We report the structural, vibrational, and electrical transport properties up to ∼16GPa of 1T-TiTe2, a prominent layered 2D system. We clearly show signatures of two isostructural transitions at ∼2GPa and ∼4GPa obtained from the minima in c/a ratio concomitant with the phonon linewidth anomalies of Eg and A1g modes around the same pressures, providing a strong indication of unusual electron-phonon coupling associated with these transitions. Resistance measurements present nonlinear behavior over similar pressure ranges shedding light on the electronic origin of these pressure-driven isostructural transitions. These multiple indirect signatures of an electronic transition at ∼2GPa and ∼4GPa are discussed in connection with the recent theoretical proposal for 1T-TiTe2 and also the possibility of an electronic topological transition from our electronic Fermi surface calculations. Between 4 GPa and ∼8GPa, the c/a ratio shows a plateau suggesting a transformation from an anisotropic 2D layer to a quasi-3D crystal network. First-principles calculations suggest that the 2D to quasi-3D evolution without any structural phase transitions is mainly due to the increased interlayer Te-Te interactions (bridging) via the charge density overlap. In addition, we observed a first-order structural phase transition from the trigonal (P3-m1) to monoclinic (C2/m) phase at higher pressure regions. We estimate the start of this structural phase transition to be ∼8GPa and also the coexistence of two phases [trigonal (P3-m1) and monoclinic (C2/m)] was observed from ∼8GPa to ∼16GPa. © 2018 American Physical Society.