In order to model the activated isotopes and resulting dose from a nuclear detonation in an urban environment, the Activation and Transmutation of Isotopes in an Unstructured Mesh (ACTIUM) Python toolkit has been developed to combine the unstructured mesh–based particle transport capability of MCNP6.2 with the CINDER2008 transmutation code to produce quantities of interest for the post-detonation nuclear forensics and weapons effects communities. The ACTIUM toolkit has been implemented and validated with a number of test cases from a simple analytic model to a case study of the urban detonation in Nagasaki, Japan. The ACTIUM approach is the first of its kind to couple the latest release of CINDER2008 as a part of the Activation in Accelerator Radiation Environments (AARE) package with MCNP6.2 and produce transmuted quantities per time step on an unstructured mesh for the nuclear forensics and weapon effects communities. ACTIUM uses the latest ENDF/B-VIII.0, TENDL2017, and JENDL4 cross-section libraries for the transmutation calculations and includes methods for producing material cards for the initial MCNP6.2 unstructured mesh calculation based on highly detailed materials often found in urban environments on a city-specific basis.