As device feature sizes shrink to nano-scale, continuous technology scaling has led to a large increase in parameter variability during semiconductor manufacturing process. According to the source of uncertainty, parameter variations can be classified into three categories: process variations, environmental variations, and temporal variations. All these variation sources exert significant influences on circuit performance, and make it more challenging to characterize parameter variability and achieve robust, low-power designs. The scope of this dissertation is conquering parameter variability and successfully designing efficient yet robust integrated circuit (IC) systems. Previous experiences have indicated that we need to tackle this issue at every design stage of IC chips. In this dissertation, we propose several robust techniques for accurate variability characterization and efficient performance prediction under parameter variations. At pre-silicon verification stage, a robust yield prediction scheme under limited descriptions of parameter uncertainties, a robust circuit performance prediction methodology based on importance of uncertainties, and a robust gate sizing framework by ElasticR estimation model, have been developed. These techniques provide possible solutions to achieve both prediction accuracy and computation efficiency in early design stage. At on-line validation stage, a dynamic workload balancing framework and an on-line self-tuning design methodology have been proposed for application-specific multi-core systems under variability-induced aging effects. These on-line validation techniques are beneficial to alleviate device performance degradation due to parameter variations and extend device lifetime.