MXenes, are a family of two-dimensional (2D) transition metal carbides, nitrides and/ or carbonitrides.[1] The intercalation of different metal cations and organic molecules into MXene for tuning MXenes’ electronic and electrochemical properties have been widely reported.[2] [3] [4] However, transition metals (TMs) which have distinct electrochemical behaviors[5] [6] have not been explored in the literature of MXenes’ intercalation. Therefore, we herein compared the intercalation effects of different TM cations on Ti3C2Tx, for offering a general insight on the influences of multi-valent, redox-active TMs on MXenes. In particular, the changes on the physiochemical and electrochemical properties of MXenes were investigated using different in-situ and ex-situ methods, for a better understanding on the interfacial interactions of TM cations and MXenes in the confined environment of MXenes’ multilayer structures. This work serves as a foundation for the fine-tuning of MXenes’ properties by utilizing a variety of TM cations intercalation for different electrochemical systems.[1] B. Anasori, M. R. Lukatskaya, Y. Gogotsi, Nature Reviews Materials 2017, 2, 16098.[2] M. R. Lukatskaya, O. Mashtalir, E. Ren Chang, Y. Dall’Agnese, P. Rozier, L. Taberna Pierre, M. Naguib, P. Simon, M.W. Barsoum, Y. Gogotsi, Science 2013, 341, 1502-1505.[3] J. Li, H. Wang, X. Xiao, Energy & Environmental Materials 2020, 3, 306-322[4] M. Ghidiu, S. Kota, J. Halim, A. W. Sherwood, N. Nedfors, J. Rosen, V. N. Mochalin, M. W. Barsoum, Chemistry of Materials 2017, 29, 1099-1106.[5] D. Göhl, H. Rueß, M. Pander, A. R. Zeradjanin, K. J. J. Mayrhofer, J. M. Schneider, A. Erbe, M. Ledendecker, Journal of The Electrochemical Society 2020, 167, 021501.[6] M. Esmaeilirad, A. Baskin, A. Kondori, A. Sanz-Matias, J. Qian, B. Song, M. Tamadoni Saray, K. Kucuk, A. R. Belmonte, P. N. M. Delgado, J. Park, R. Azari, C. U. Segre, R. Shahbazian-Yassar, D. Prendergast, M. Asadi, Nature Communications 2021, 12, 5067.