Under the real and evolving manufacturing conditions, lithography hotspot detection faces many challenges. First, real hotspots become hard to identify at early design stages and hard to fix at post-layout stages. Second, false alarms must be kept low to avoid excessive and expensive post-processing hotspot removal. Third, full chip physical verification and optimization require very fast turn-around time. Last but not least, rapid technology advancement favors generic hotspot detection methodologies to avoid exhaustive pattern enumeration and excessive development/update as technology evolves. To address the above issues, we propose a high performance hotspot detection methodology consisting of: 1) a fast layout analyzer; 2) powerful hotspot pattern identifiers; and 3) a generic and efficient flow with successive performance refinements. We implement our algorithms with industry-strength engine under real manufacturing conditions and show that it significantly outperforms state-of-the-art algorithms in false alarms (2.4X to 2300X reduction) and runtime (5X to 237X reduction), meanwhile achieving similar or better hotspot accuracies. Compared with pattern matching, our method achieves higher prediction accuracy for hotspots that are not previously characterized, therefore, more detection generality when exhaustive pattern enumeration is too expensive to perform a priori. Such high performance hotspot detection is especially suitable for lithography-friendly physical design.