Purpose: It is possible to combine theoretical models with Monte Carlo simulations to investigate the relationship between radiation-induced initial DNA damage and cell survival. Several combinations of models have been proposed in recent years, sparking interest in comparing their predictions in view of future clinical applications. Methods: Two in silico methods for calculating cell survival fractions were optimized for proton irradiation of the Chinese hamster V79 cell line, for LET values ranging from 3.40 and 100 keV/mu m. These methods, based on different Monte Carlo codes and theoretical models, were benchmarked against published V79 cell survival data to identify the sources of discrepancies. Results: The predictive capacities of the methods were evaluated for several proton LET values using an external dataset. After recalibrating model parameters, multiple methods were assessed. This approach helped identify sources of variation, the main one being the simulated number of DSBs, which differed by a factor up to 3 between the two Monte Carlo codes. In this process anew method was defined, that, in all but one case, allows fora reduction in prediction error of up to 56%. Additionally, a freely available GUI for computing cell survival was refined, to facilitate further comparison of diverse theoretical models. Conclusion: The systematic comparison of two predictive chains, characterized by distinct applicability ranges and features, was conducted. Optimization and analysis of various combinations were undertaken to elucidate differences. Addressing and minimizing such discrepancies will be crucial for further enhancing the reliability of predictive models of cell survival, aiming for biologically informed treatment planning.