In this review, we summarize the recent design strategies (2015–present) of nanomaterial-based vaccine delivery systems via multiple routes to induce robust protective immunity. The selected topics are focused on the novel design strategies of nanomaterial carriers for vaccine delivery. Inspired by recent advances, we also briefly introduce the emerging administration routes that may give rise to synergistic immune effects with advanced delivery systems. Ultimately, we present the existing challenges and survey the prospective development of various nanoparticle vaccine delivery systems.