Based on the common properties exhibited in both cuprates and iron-based high temperature superconductors, we have recently proposed the “gene” concept for unconventional high temperature superconductors: those d-orbitals of transition metal elements with the strongest in-plane bonding to anion p-orbitals must be isolated near Fermi energy. Here we summarized recent progress in this research direction and discussed several electronic environments that meet the “gene” condition. We also discussed the challenge and the possibility in finding new unconventional high temperature superconductors.