The growing history of the Milky Way has been tightly imprinted into the elemental abundances of the interstellar medium, especially for the isotopes of Carbon, Nitrogen, and Oxygen, due to their different origins of parental stars. The ratios of these CNO isotopes have been well known as their systematic gradients from the inner Galaxy to the outer disk, which, in turn, set constraints on the star-formation history and stellar models. However, current CNO isotope gradients are still limited to Galactocentric radius Rgc <~ 10 kpc, leaving out the metal-poor Galactic outer disk region. Here we present a deep 3-mm and 2-mm line survey towards 15 metal-poor molecular clouds on the Galactic outer disk, up to Rgc ~ 22 kpc, with the IRAM 30-m telescope. Using updated distances from VLBI, corrections of the cosmic microwave background, and the full Planck expression in deriving physical parameters, we obtained new Galactic gradients of ratios of C-12/C-13, O-16/O-18, O-18/O-17, and N-14/N-15, reaching the low metallicity regime of the Milky Way. These new data suggest that massive rotator and novae may play a non-neglectable role in the chemical enrichment, which still needs more detailed work with Galactic chemical evolution models.