The trend towards multi-/many- core design has made network-on-chip (NoC) a crucial component of future microprocessors. With CMOS processing technologies continuously scaling down to the nanometer regime, effects such as process variation (PV) and negative bias temperature instability (NBTI) significantly decrease hardware reliability and lifetime. Therefore, it is imperative for multi-core architects to consider and mitigate these effects in NoCs implemented using small-scale processing technology. This paper reports on a first step to optimize NoC architecture reliability in light of both PV and NBTI effects. We propose novel techniques that can hierarchically alleviate PV and NBTI effects on NoC while leveraging their benign interaction. Our low-level design improves PV and NBTI efficiency of key components (e.g. virtual channel allocation logics, virtual channels) of critical paths of the pipelined router microarchitecture. Our high-level mechanisms leverage NBTI degradation and PV information from multiple routers to intelligently route packets, delivering optimized performance-power-reliability across the NoC substrate. Experimental results show that our intra-router level techniques (i.e. VA_M1 and VC_M2) reduce guardband by 47% while improving network throughput by 24%. Our inter-router optimization scheme (i.e. IR_M3) results in 50% guardband reduction and 19% network latency improvement.