This document discusses the challenges of engineering large, socio-technical systems where there are significant unknown factors (LSCITS). It argues that the traditional reductionist approach to engineering breaks down for these systems. LSCITS engineering must account for scale, uncertainty, and the entanglement of social and technical aspects. Some key challenges identified include managing large scale systems, dealing with uncertainty, reasoning about complex systems, integrating different systems, and developing standards for LSCITS. The document advocates an approach that tempers reductionism with pragmatism and recognition of real-world constraints like imperfect people and organizations.