Transition metal oxides form a series of compounds with a uniquely wide range of electronic properties. Some have been known since antiquity, whereas other properties, such thermoelectricity (TE) have been discovered rather recently. In developing such material systems, Mn, Cu, Co or Ni oxides and their binary combinations were considered for thermoelectric applications over forty years ago at the Westinghouse Research Laboratory [1,2]. Complex quaternary compositions can potentially deliver more flexibility in terms for structural variations and their transport mechanisms, anticipating better performance for thermoelectric properties . Over a wide range of compositions, containing Mn, Cu, Ni, and Co, the crystal structure basically takes on the spinel (AB2O4) configuration, where oxygen tetrahedrally coordinates A-sites and octahedrally coordinates the B-sites; however, the unit cell contains 56 atoms with 8 A-site atoms, 16 B-site atoms, and 32 oxygen atoms. Electrical conduction in similar oxide compounds has been shown to originate from a charge hopping mechanism: either variable range hopping or small-polaron hopping [4,5]. A small-polaron is a charge that resides on a cation but has a wave function extending beyond that of a normal valence electron. The potentially delocalized nature of this charge combined with the strain field generated by the neighboring atoms has two defining characteristics of a polaron [6, 7]. The consensus is that hopping occurs between the Mnoccupied B-sites of the unit cell, and these sites lie along the <110> directions. The hopping between adjacent B-B sites provides the shortest inter-site gaps, as compared to the A-B or A-A inter-site distances. Current thermoelectric materials are suited to room temperature applications, yet it remains highly desirable to identify new materials that function efficiently at elevated temperatures. Oxides are a natural choice due to their high temperature stability. In an attempt to develop complex multi-component oxide systems having specific properties for thermoelectric applications, we describe here our strategy in finding optimum compositions through “combinatorial material search (CMS)”. Once the desired compositions are selected, the materials are then fabricated by low temperature synthesis, stabilizing thermodynamically metastable valence states of the ions. The present study was aimed at finding material’s compositions having unique thermoelectric properties; however, the strategy described here can be used, in general, to search new material systems for specific applications of interest. The application of CMS, originally developed by Xiang and Schultz , promises to increase an ability to identify and optimize the material compositions and their properties in a very efficient way. We have recently demonstrated an effective use of CMS on a Ni-Cu-Mn based oxide system. Experimentally, three target materials (NiO, CuO and Mn2O3) were sequentially deposited in thin film forms using a pulsed laser deposition (PLD) technique, in which thickness of the each layer was tapered over the substrate. After sequentially depositing three material layers, the process was repeated for multiple rounds until desired thickness is achieved on the substrate. By proper annealing, three materials were mutually diffused to form continuously graded ternary compositions on the substrate. In Fig. 1, the CMS process is schematically illustrated.