Adopting a case study methodology with mixed methods data collection and analysis, this study investigates causes and mitigation strategies related to urban informal settlement and infrastructure (UISI) in Hong Kong Special Administrative Region (SAR), Seattle, Washington, United States and Lagos metropolis, Nigeria. The study indicates that informal urban settlement is associated with factors including socio-economics, environmental conditions, and governance. In Lagos metropolis, UISI stems from inadequate infrastructural development, economic challenges, governance and other factors. In Seattle and Hong Kong, the escalating cost of living (housing) and a widening gap between the rich and the poor create homelessness and street sleepers which contributes to UISI. In Seattle, significant efforts and resources are directed towards this urban threat. However, administrative bureaucracy, inadequate coordination of organizations and issues of equality, equity, and race hinder significant advancements. The study recommends policy reforms, community-based participatory design, and inclusive socio-economic and environmental planning design as vehicles for sustainable development.