Molecular engineering is a unique methodology to take advantage of the electrochemical characteristics of materials that are used in energy-harvesting devices. Particularly in triboelectric nanogenerator (TENG) studies, molecular grafting on dielectric metal oxide surfaces can be regarded as a feasible way to alter the surface charge density that directly affects the charge potential of triboelectric layers. Herein, we develop a feasible methodology to synthesize organic–inorganic hybrid structures with tunable triboelectric features. Different types of self-assembled monolayers (SAMs) with electron-donating and withdrawing groups have been used to modify metal oxide (MO) surfaces and to modify their charge density on the surface. All the synthetic routes for hybrid material production have been clearly shown and the formation of covalent bonds on the MO’s surface has been confirmed by XPS. The obtained hybrid structures were applied as dopants to distinct polymer matrices with various ratios and fiberization processes were carried out to the prepare opposite triboelectric layers. The formation of the fibers was analyzed by SEM, while their surface morphology and physicochemical features have been measured by AFM and a drop shape analyzer. The triboelectric charge potential of each layer after doping and their contribution to the TENG device’s parameters have been investigated. For each triboelectric layer, the best-performing tribopositive and tribonegative material combination was separately determined and then these opposite layers were used to fabricate TENG with the highest efficiency. A comparison of the device parameters with the reference indicated that the best tribopositive material gave rise to a 40% increase in the output voltage and produced 231 V, whereas the best tribonegative one led to a 33.3% rise in voltage and generated 220 V. In addition, the best device collected ~83% more charge than the reference device and came up with 250 V that corresponds to 51.5% performance enhancement. This approach paved the way by addressing the issue of how molecular engineering can be used to manipulate the triboelectric features of the same materials.