A fully connected “deep” neural network algorithm with the Community Radiative Transfer Model (FCDN_CRTM) is proposed to explore the efficiency and accuracy of reproducing the Visible Infrared Imaging Radiometer Suite (VIIRS) radiances in five thermal emission M (TEB/M) bands. The model was trained and tested in the nighttime global ocean clear-sky domain, in which the VIIRS observation minus CRTM (O-M) biases have been well validated in recent years. The atmosphere profile from the European Centre for Medium-Range Weather Forecasts (ECMWF) and sea surface temperature (SST) from the Canadian Meteorology Centre (CMC) were used as FCDN_CRTM input, and the CRTM-simulated brightness temperatures (BTs) were defined as labels. Six dispersion days’ data from 2019 to 2020 were selected to train the FCDN_CRTM, and the clear-sky pixels were identified by an enhanced FCDN clear-sky mask (FCDN_CSM) model, which was demonstrated in Part 1. The trained model was then employed to predict CRTM BTs, which were further validated with the CRTM BTs and the VIIRS sensor data record (SDR) for both efficiency and accuracy. With iterative refinement of the model design and careful treatment of the input data, the agreement between the FCDN_CRTM and the CRTM was generally good, including the satellite zenith angle and column water vapor dependencies. The mean biases of the FCDN_CRTM minus CRTM (F-C) were typically ~0.01 K for all five bands, and the high accuracy persisted during the whole analysis period. Moreover, the standard deviations (STDs) were generally less than 0.1 K and were consistent for approximately half a year, before they significantly degraded. The validation with VIIRS SDR data revealed that both the predicted mean biases and the STD of the VIIRS observation minus FCDN_CRTM (V-F) were comparable with the VIIRS minus direct CRTM simulation (V-C). Meanwhile, both V-F and V-C exhibited consistent global geophysical and statistical distribution, as well as stable long-term performance. Furthermore, the FCDN_CRTM processing time was more than 40 times faster than CRTM simulation. The highly efficient, accurate, and stable performances indicate that the FCDN_CRTM is a potential solution for global and real-time monitoring of sensor observation minus model simulation, particularly for high-resolution sensors.