Integrating millions of transistors and their associated interconnections on very large-scale integration (VLSI) chip leads to significant process variations during fabrication. Identification and analysis of these process-induced variations are significantly important during the prefabrication step in VLSI flow. Variability analysis of on-chip interconnect plays a vital role in predicting the reliability and robustness of the interconnect system. The current chapter determines the variability impact of various devices and interconnects on the system performance using driver-interconnect-load (DIL) model. The parametric, process corner, and Monte Carlo variability analysis have been performed. Carbon nanotubes have been proven a superior alternative to traditional semiconductor materials for transistors and conducting materials for on-chip interconnects. Hence, various variability analyses have been carried out for different combinations of silicon and carbon nanotube field effect transistor (CNTFET) based CMOS driver-load with both copper and multiwall CNT bundle (MWCNTB) interconnects. It is interpreted that the combination of CNTFET based driver-load with CNT bundle interconnects provides better performance than the conventional Si-based driven copper interconnects.