— This work investigates three aspects: (a) a network vulnerability as the non-uniform vulnerable-host distribution, (b) threats, i.e., intelligent worms that exploit such a vulnerability, and (c) defense, i.e., challenges for fighting the threats. We first study five data sets and observe consistent clustered vulnerablehost distributions. We then present a new metric, referred to as the non-uniformity factor, which quantifies the unevenness of a vulnerable-host distribution. This metric is essentially the Renyi information entropy and better characterizes the non-uniformity of a distribution than the Shannon entropy. We then analytically and empirically measure the infection rate and the propagation speed of network-aware worms. We show that a representative network-aware worm can increase the spreading speed by exactly or nearly a non-uniformity factor when compared to a randomscanning worm at the early stage of worm propagation. This implies that when a worm exploits an uneven...