The different generations of calc-silicate assemblages formed during sequential metasomatic events make the Campiglia Marittima magmatic–hydrothermal system a prominent case study to investigate the mobility of rare earth element (REE) and other trace elements. These mineralogical assemblages also provide information about the nature and source of metasomatizing fluids. Petrographic and geochemical investigations of granite, endoskarn, and exoskarn bodies provide evidence for the contribution of metasomatizing fluids from an external source. The granitic pluton underwent intense metasomatism during post-magmatic fluid–rock interaction processes. The system was initially affected by a metasomatic event characterized by circulation of K-rich and Ca(-Mg)-rich fluids. A potassic metasomatic event led to the complete replacement of magmatic biotite, plagioclase, and ilmenite, promoting major element mobilization and crystallization of K-feldspar, phlogopite, chlorite, titanite, and rutile. The process resulted in significant gain of K, Rb, Ba, and Sr, accompanied by loss of Fe and Na, with metals such as Cu, Zn, Sn, W, and Tl showing significant mobility. Concurrently, the increasing fluid acidity, due to interaction with Ca-rich fluids, resulted in a diffuse Ca-metasomatism. During this stage, a wide variety of calc-silicates formed (diopside, titanite, vesuvianite, garnet, and allanite), throughout the granite body, along granite joints, and at the carbonate–granite contact. In the following stage, Ca-F-rich fluids triggered the acidic metasomatism of accessory minerals and the mobilization of high-field-strength elements (HFSE) and REE. This stage is characterized by the exchange of major elements (Ti, Ca, Fe, Al) with HFSE and REE in the forming metasomatic minerals (i.e., titanite, vesuvianite) and the crystallization of HFSE-REE minerals. Moreover, the observed textural disequilibrium of newly formed minerals (pseudomorphs, patchy zoning, dissolution/reprecipitation textures) suggests the evolution of metasomatizing fluids towards more acidic conditions at lower temperatures. In summary, the selective mobilization of chemical components was related to a shift in fluid composition, pH, and temperature. This study emphasizes the importance of relating field studies and petrographic observations to detailed mineral compositions, leading to the construction of litho-geochemical models for element mobilization in crustal magmatic-hydrothermal settings.