Throughout the development of radio-pharmaceuticals, metal complexes have been applied for diagnose of various diseases in the world. As a relatively new area, technetium-99m radionuclides labeled sophisticated chelateing agents to produce diagnostic radiopharmaceuticals have gained more and more attention in vivo specific imaging. Since the use of ⁹⁹Mo-^99mTc generator as a significant marker of ^99mTc chemistry, it has been widely studied and described on the chemical and structural properties of ^99mTc-complexes with different sizes, lipophilicity and charges, in addition of their biodistribution and targeting capabilities. Focus has taken place on the progress of developing technetium-99m labeled drugs in order to optimize the future performance in gamma-emitting diagnostic radio-pharmaceutical domain. It is discussed and suggested in this review that an immense space occurs for further development of target-specific imaging agents, especially drugs produced from biomolecules labeled by ^99mTc.