Based on the integration of U-Pb isotopic data, geochemical data, petrographic data and geological data of the Neoproterozoic granitic and metavolcanic rocks of southernmost ANS, Northern Ethiopia, western shire district, the following conclusions can be drawn: (1) The study area consists of low-grade metavolcano-sedimentary rock assemblages that belong to the Tsaliet and Tambien Groups of the Arabian-Nubian Shield. Six major lithological units have been identified in the area and include mainly metavolcanics, sericite quartz-feldspar schist, phyllitic and graphitic schist, mafic -ultramafic rocks, sedimentary rocks, and granitic intrusives. The main mineralizations are placer gold and volcanogenic massive sulfides. The granite suites are dominantly represented by grey and pink granites, which are traversed by younger aplitic dikes, basic dikes (dolerite dike) which are common character of I-type granites. The wide spread occurrence of mafic enclaves in the granitic plutons (presence of dark colored xenoliths) suggest their derivation from mantle. (2) Petrographically, the groundmass of the rock samples is mainly composed of plagioclase, quartz, and K-feldspars (Microcline, perthitic), biotite and secondary muscovite, hornblende. Accessory minerals include; zircon, allanite, apatite, rutile, titanite, pyrite and common Fe-Ti oxides (Ilmenite and magnetite). (3) Zircon and titanite U-Pb age dates indicate that the Hitsas pluton is emplaced at about 627.5 ± 1.1 Ma, that of the Gurungur granite is at about 624.24±0.60Ma, and that of the Kisad Gaba granite is at about 606.1 ± 2.6 Ma and 610.7 ± 1.1Ma coeval with the juvenile Neoproterozoic rocks in the ANS. All the zircon grains were free of inheritance/inherited zircon cores/, which is an important feature of S-type granites (Clemens, 2002). This lack of inheritance confirms that the studied granites are clearly I-type. (4) The geochemical data indicates that the higher Na2O/K2O ratios (0.08-1.51) and higher K2O/ Na2O ratios (0.97-1.55; Table 2) suggest that the samples are K2O and Na2O dominated, with the predominance of K2O over Na2O. The P-poor (P2O5<0.13wt %), high SiO2 (67.21-75.51), high total alkali concentration (8.22-8.97wt %) and show high-K calc-alkaline affinity formed during volcanic arc magmatism/subduction related / environments. The high SiO2, (Na2O + K2O), and Al2O3, low MgO, Fe2O3, and CaO concentrations imply that the primary magma was derived from partial melting that involves lower crust. The compositional trends of the granites and metavolcanic rocks indicate a decrease in Al2O3, Fe2O3, MgO, CaO, TiO2, P2O5, with increasing SiO2, which might be due to the fractionation of plagioclase or biotite or crustal contamination of magmas during magmatic emplacement. (5) The constructed discrimination diagrams and spider diagrams together with the geochemical characteristics of high-K calcalkaline affinity, their I-type and S-type character with strongly peraluminous (A/CNK= 1.36-1.46 in the granites and 2.77 in the metavolcanic), the enrichment of large ion lithophile elements, depletion in high field strength elements (Nb, Ta and Ti) and P signifying a magmatic tectonics above subduction zones of volcanic arc and syn to post-collisional granitoids. (6) Thus based on the integration of the geological data, geochemical data and geochronological (U-Pb zircon and titanite) data the studied granites and metavolcanic rocks are typically Neoproterozoic I-type and have S-type characteristics with strongly peraluminous nature at western Shire (Hitsas, Gurungur and Kisad Gaba areas). They are generated from a mixed mantle-crust source. The negative Nb, Ti, and P anomalies most probably formed by partial melting of crustal materials or magma mixing (juvenile crust) or indicate a subduction zone related origin. The I-type granitoids are also enriched in Ba, K, Th, and U and depleted in Nb indicating they had interaction with the crust. I-type granitoids might result from contamination of mantle derived magmas by continental crust materials above subduction zones or volcanic arc, evidenced by the wide spread occurrence of mafic enclaves in the granitic plutons.