In this investigation, the effects of \(Nd\) substitution on the structural, morphological, magneto-electrical transport, and magnetic properties in the La0.8-xNdxCa0.15Sr0.05MnO3 (x = 0.0, 0.05, 0.10, and 0.20) synthesized via the solid-state reaction were reported. The Rietveld X-ray diffraction (XRD) patterns refinement revealed a Pnma orthorhombic structure. Scanning electron microscopy (SEM) coupled with energy-dispersive X-ray (EDX) spectroscopy revealed a micro-granular morphology with slight variations in average grain size ( \({D}_{SEM}\) ) upon \(Nd\) substitution, ranging from 1.19 μm for x = 0.10 to 1.78 μm for x = 0.20. EDX analysis confirmed the presence of all expected constituting elements. The temperature-dependent electrical resistivity, \(\rho \left(T\right)\) , exhibited a metal-to-insulator transition at \({T}_{MI}\) which gradually decreased with increasing \(Nd\) content. \(Nd\) substitution significantly enhanced magnetoresistance (MR), yielding a maximum \(MR\%\) of \(48\%\) at \(T=214 K\) near \({T}_{MI}\) for the x = 0.10 sample under one tesla. The temperature coefficient of the resistivity ( \(TCR\%\) ) showed similar trends, reaching a peak value of 6.30% K−1 for the x = 0.05 sample. For \(T<{T}_{MI}\) , the fitting of resistivity data indicates that the transport mechanism is governed by grain boundary effects, electron–electron scattering, and electron–phonon interactions. For \(T> {T}_{MI}\) , the data are well described by both the Adiabatic Small Polaron Hopping (ASPH) and 3D-Variable Range Hopping (3D-VRH) mechanisms. The obtained values of density of states \(N\left({E}_{F}\right)\) were found to be in the order of 1019 eV−1.cm−3. The mean hopping distance and the mean hopping energy, extracted from the 3D-VRH model, were found to lie in the ranges of 2.57–3.78 nm and 0.1–0.14 eV, respectively. Magnetization measurements \(M\left(T,H\right)\) indicated a ferromagnetic-to-paramagnetic transition at the Curie temperature, \({T}_{C}\) . The decrease in \({T}_{C}\) and \({T}_{MI}\) with increasing \({Nd}^{3+}\) concentration was attributed to the weakening of double-exchange interactions between \({Mn}^{3+}\) and \({Mn}^{4+}\) ions.