We report our recent study on the pulsed laser deposition process in the synthesis of colossal magnetoresistive MgO/LaCaMnO3 and MgO/LaSrMnO3 core-shell nanowires. A highly efficient process has been developed by depositing an epitaxial layer of manganite onto randomly oriented MgO nanowires grown on SiO2/Si substrates. In addition, in-depth studies revealed that the sample-target distance played a critical role in determining the core-shell nanowire quality. The MgO/LaCaMnO3 and MgO/LaSrMnO3 nanowires opened up the unique opportunity to explore a number of intriguing physical properties at the nanoscale. Remarkable metal-insulator phase transitions and pronounced colossal magnetoresistance have been observed in both LaCaMnO3 and LaSrMnO3 nanostructures.