Nanoscale computing systems show great potential but at the same time introduce new challenges not encountered in the world of conventional CMOS designs and manufacturing. For example, these systems need to work around layout and doping constraints resulting from unconventional bottom-up selfassembly, and need to cope with high manufacturing defect rates and transient faults. Unfortunately, most conventional defecttolerance techniques are not directly applicable in nanoscale systems because they have been designed for very small defect rates. In this paper, we explore built-in defect-tolerance techniques on 2-D semiconductor nanowire (NW) arrays to make designs self-healing. Our approach combines circuit and systemlevel techniques and it does not require defect map extraction, reconfigurable devices, or addressing each cross-point similar to reconfigurable approaches. We show that a defect-tolerant simple processor based on our approach would be still around 3X denser than an 18-nm CMOS version with equivalent functionality; a yield greater than 30% is achieved despite a fabric with 14% defective FETs.