Effective integration of human factors and systems engineering has become a technical challenge that constrains the full realization of human performance in unmanned aircraft systems (UAS) for urban air transportation. To address this challenge, breakthroughs are needed in key technologies related to human-system integration (HSI) of UAS. Based on literature review and industry practices, unique HF challenges of UAS are identified, and two research issues, HSI analysis throughout UAS development lifecycle and HSI practice under UAS typical lifecycle stages, are summarized. To address these issues, a model-based human-system integration (MBHSI) design framework is proposed for the UAS development lifecycle, along with an HSI practice framework for UAS under typical human readiness levels. The HSI design and practice framework can provide references for HF design of UAS in urban air transportation.