In many developing countries, including South Africa, water scarcity has resulted in poor sanitation practices. The majority of the sanitation infrastructures in those regions fail to meet basic hygienic standards. This along with the lack of proper sewage/wastewater infrastructure creates significant environmental and public health concerns. A self-sustained, waterless “Nano Membrane Toilet” (NMT) design was proposed as a result of the “Reinvent the Toilet Challenge” funded by the Bill and Melinda Gates Foundation. A “cradle-to-grave” life cycle assessment (LCA) approach was adopted to study the use of NMT in comparison with conventional pour flush toilet (PFT) and urine-diverting dry toilet (UDDT). All three scenarios were applied in the context of South Africa. In addition, a Quantitative Microbial Risk Assessment (QMRA) was used to reflect the impact of the pathogen risk on human health. LCA study showed that UDDT had the best environmental performance, followed by NMT and PFT systems for all impact categories investigated including human health, resource and ecosystem. This was mainly due to the environmental credits associated with the use of urine and compost as fertilizers. However, with the incorporation of the pathogen impact into the human health impact category, the NMT had a significant better performance than the PFT and UDDT systems, which exhibited an impact category value 4E + 04 and 4E + 03 times higher, respectively. Sensitivity analysis identified that the use of ash as fertilizer, electricity generation and the reduction of NOx emissions were the key areas that influenced significantly the environmental performance of the NMT system.