Mpox has evolved into a global public health concern following rapid geographic expansion and altered clinical and epidemiological characteristics. The 2022 outbreak of monkeypox virus (MPXV) marked the first widespread expansion to non-endemic regions, particularly among men who have sex with men (MSM). In the Democratic Republic of the Congo (DRC), where Clade I MPXV is endemic, data on urban exposures are limited. We evaluated serologic evidence of exposure using a four-plex MPXV assay among 1,823 participants from two major DRC cities, Kinshasa and Goma, between April and June 2024. Of these participants, 523 (28.7%) self-identified as MSM, 498 (27.3%) as professional sex workers (SW), 107 (5.9%) as MSM and SW, and 695 (38.1%) as other at-risk individuals. Overall, 2.9% of participants were seroreactive. By subpopulation, 4.8%, 2.1%, and 1.7% of at-risk, MSM, and SW participants were seroreactive (p = 0.0086). Classification tree modelling identified age as the strongest predictor of reactivity, with higher MPXV seroreactivity in older participants. These data provide evidence of mpox seroreactivity prior to sustained human-to-human transmission in urban settings. Understanding exposure dynamics is critical for anticipating re-emergence of mpox in global cities where interpersonal networks may sustain transmission even in the absence of zoonotic spillover.