Asynchronous Time Local Positioning Systems are emerging as a decisive tool for high-demanded accuracy applications. Its relevance relies on the unnecessary synchronism of the system devices and the ad-hoc node deployment for fitting the design requirements in irregular scenarios. In this paper, we provide a new methodology for obtaining optimized cost-effective asynchronous node deployments based on system accuracy, enhanced primary and emergency operating conditions and security robustness. In addition, we perform a deep analysis of the NP-Hard node location problem and we propose a new Cramér-Rao Bound (CRB) error characterization considering Line-of-Sight (LOS) and Non-Line-of-Sight (NLOS) system connections and clock instabilities for evaluating the quality of a node deployment. We apply a Genetic Algorithm optimization in an irregular scenario of simulations to display this innovative methodology with a trade-off between resolution in the search in the space of solutions and the achievement of time-effective results. Results show that deployments with 4 and 5 coordinator sensors fulfill the design requirements in the proposed scenario in both primary and emergency conditions (1.14 and 1.70 meters and 0.89 and 1.47 meters of mean errors respectively) while 5 coordinator sensor configurations outperform 4 coordinator sensor configurations in system security robustness proving their preeminence in this study.