Background: American cutaneous leishmaniasis (ACL) is endemic in central Panama, where rapid land use change is transforming tropical landscapes and potentially altering the ecology of sand fly vectors. Although researchers have widely studied environmental determinants of individual vector species, community-level responses of sand fly assemblages to landscape modification remain poorly understood. We evaluated how landscape composition, fragmentation, climate, and topography influence sand fly community structure in a rural landscape of central Panama. Methodology/Principal Findings: We combined metacommunity analyses with joint species distribution models (JSDMs) to quantify species-specific and community-level responses to climatic variables, land-cover composition, and forest configuration. We collected 1,692 individuals representing 30 species, including nine anthropportunist taxa of epidemiological importance. Sand fly assemblages had strong nestedness, low species turnover, and predominantly positive residual associations. Several anthropportunist sand fly species occurred across heterogeneous landscapes, although their responses to environmental conditions differed among taxa. Land-cover composition, forest fragmentation metrics, and elevation together explained about half of the variance in species occurrence and abundance, with the remainder attributed to climate and spatial, temporal, and community-level random effects. Grassland cover contributed most strongly to sand fly occurrence and abundance, whereas artificial surfaces consistently reduced both metrics. Fragmentation effects varied by species: edge density often increased occurrence and abundance, whereas more forest patches generally suppressed populations. Increased precipitation broadly enhanced occurrence and abundance, whereas higher temperatures negatively affected several taxa. Conclusions/significance: Landscape heterogeneity predictably structures sand fly communities, and different forms of anthropogenic disturbance exert non-uniform effects on vector assemblages. The nested organization of these assemblages and the co-occurrence of several anthropophilic species suggest that multiple potential vector species may be present across heterogeneous landscapes. These findings highlight the need for landscape-informed surveillance and control strategies that prioritize grassland–forest interfaces and other disturbed ecotones where sand fly species of epidemiological importance frequently co-occur.