Previous studies of the mid-Cretaceous (ca. 85 Ma) LCT-type Little Nahanni Pegmatite Group (LNPG; Northwest Territories, Canada) document disequilibrium textures and pervasive metasomatism associated with rare-metal (e.g., Ta, Nb, Sn) mineralization. As in other pegmatite settings, the source of the melts and the nature and origin of pervasive metasomatism remain enigmatic. To resolve these latter issues, an integrated study of bulk O and H isotope analysis of mineral separates (quartz, K-feldspar, albite, muscovite, garnet), in situ Secondary Ion Mass Spectrometry (SIMS) isotopic (O) analysis of quartz and albite, and in situ Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) trace element analysis of quartz was done in concert with cathodoluminescence (CL) imaging and petrographic observations. Quartz with elevated δ18O values (δ18Oquartz = 10 to 16.3‰) also have high Ti-in-quartz temperatures (551 ± 17 °C to 603 ± 16 °C). These data along with their pristine nature from CL imaging suggest some localized melt-wall rock (WR) exchange occurred at the time of pegmatite melt emplacement. Furthermore, the elevated δ18O values indicate a crustal source (i.e., S-type granite) for the LNPG parental melt, which also overlaps with δ18Oquartz data for granitoids of the mid- to Late-Cretaceous Selwyn Plutonic Suite of this area. In contrast, the large range for δ18O values for metasomatic minerals, such as albite (−3.0 to +18.3‰) indicate a complex evolution involving multiple oxygen isotopic reservoirs, in particular incursion of meteoric water previously equilibrated with metasedimentary wall rocks. Finally, the large range for mineral pairs (e.g., Δquartz-albite = −5.1 to +14.3‰) and abundance of dissolution features in late-stage assemblages unequivocally indicates that sub-solidus fluid:rock interaction was responsible for such large spreads in δ18O and values δD values, although other processes (e.g., disequilibrium crystallization, thermal gradients, rapid cooling) might have also contributed, but to lesser extents.