We report strategies of enhancing the ionic conductivity of triple-layered Ruddlesden-Popper oxides through design and synthesis of seven compounds belonging to the series A(2)A'2B3O10 (A = Li, A' = La, B = Ti/Nb), investigated by neutron diffraction, impedance spectroscopy, and dielectric analyses. We demonstrate, for the first time, that lithium diffusion in triple-layered Ruddlesden-Popper oxides is a result of cooperative effect of both inter- and intrastack sites, i.e., A and A'. As shown by neutron diffraction, the structure of these materials comprises triple-layered stacks of octahedra (BO6), separated by A-site cations, while A' ions reside in intrastack spaces. We first synthesized Li2La2Ti3O10 and showed that its lithium-ion conductivity can be systematically enhanced by incorporation of cation deficiency in interstack sites through synthesis of Li1.9La2Ti2.9Nb0.1O10, Li1.8La2Ti2.8Nb0.2O10, and Li1.75La2Ti2.75Nb0.2.5O10. The latter represents the limit of cation deficiency on the A-site and has the highest conductivity among the A-site-deficient materials. We then investigated the enhancement of lithium-ion conductivity by incorporation of cation defects in intrastack A'-sites through synthesis of Li(2)La(1.9)Ti(2.7)Nb(0.3)O(10 )and Li2La1.8Ti2.4Nb0.6O10, where the latter represents the limit of cation deficiency on the A'-site and has the best conductivity among the A'-deficient materials. Finally, we hypothesized that cooperative effect of defects in both inter- and intrastack sites should have an even higher impact on ionic conductivity. This hypothesis was confirmed by synthesis of Li1.9La1.9Ti2.6Nb0.4O10, which showed the highest conductivity among all materials synthesized in this work. Detailed analysis of real and imaginary components of impedance spectroscopy, as well as dielectric and loss tangent, have been conducted. This systematic study is aimed at answering a fundamental question related to materials chemistry of Ruddlesden-Popper oxides, namely, determination of the sites that contribute to ionic conductivity.