In this contribution, we present a highly accurate approach for real-time thickness measurements of multilayered coatings using terahertz time domain spectroscopy in reflection geometry. The proposed approach combines the benefits of a model-based material parameters extraction method to calibrate the specimen under test, a generalized modeling method to simulate the terahertz radiation behavior within arbitrary thin films, and the robustness of a powerful evolutionary optimization algorithm to increase the sensitivity and the precision of the minimum thickness measurement limit. Furthermore, a novel self-calibration model is introduced, which takes into consideration the real industrial challenges such as the effect of wet-on-wet spray in the car painting process and the influence of the spraying conditions and the sintering process on ceramic thermal barrier coatings (TBCs) in aircraft industry. In addition, the developed approach enables for some applications the simultaneous determination of the complex refractive index and the coating thickness. Hence, a pre-calibration of the specimen under test is not required for such cases. Due to the high robustness of the self-calibration method and the genetic optimization algorithms, the approach has been successfully applied to resolve individual layer thicknesses within multi-layered coated samples down to less than 10 µm. The regression method can be applied in time-domain, frequency-domain or in both the time and frequency-domain simultaneously. The data evaluation uses general-purpose computing on graphics processing units and thanks to the developed highly parallelized algorithm lasts less than 300 ms. Thus, industrial requirements for fast thickness measurements with an “every-second-cycle” can be fulfilled.