The higher education context that our CUMU institutions must navigate is complex and begets challenges resulting from the distinct mission our institutions seek to uphold. The implications of these challenges give rise to impacts on everyone within the institution and consequently our constituents within the cities we seek to serve. Bringing together literature, emerging research, and points from discussions at the 2016 CUMU conference, this paper analyzes challenges and their implications and highlights the strategies being employed to navigate them. We consider the tensions inherent in the urban-serving university identity, the cost of serving urban regions, and the state structures that provide funding. All of these tensions have implications for commitment to mission, access for historically marginalized students, and the experiences of faculty within the institution. We also discuss strategic initiatives and efforts that reflect collaboration, strategic alignment, and innovation. This work is of value for those working within urban-serving universities, those who work to uphold their mission in higher education, and policy makers that shape the context of these institutions’ work.