The economic return for peanut (Arachis hypogaea L.) in Ghana is often low due to limitations in the availability of inputs or their adoption, which are needed to optimize yield. Six experiments were conducted in Ghana in 2020 and 2021 to determine the impact of planting date, cultivar, fertilization, pest management practices, and harvest date on peanut yield, financial return, and pest reaction. A wide range of interactions among these treatment factors were often observed for infestations of aphids (Aphis gossypii Glover); groundnut rosette disease (Umbravirus: Tombusviridaee); millipedes (Peridontopyge spp.); white grubs (Schyzonicha spp.); wireworms (Conoderus spp.); termites (Microtermes and Odontotermes spp.); canopy defoliation as a result of early leaf spot disease caused by Passalora arachidicola (Hori) and late leaf spot caused by Nothopassalora personata (Berk. and M. A. Curtis); and the scarification and boring of pods caused by arthropod feeding. Pod yield and economic return increased for the cultivar Chitaochi and Sarinut 2 when fertilizer was applied and when fertilizer was applied at early, mid-, and late planting dates. Pod yield and economic return increased when a combination of locally derived potassium soaps was used for aphid suppression and one additional hand weeding was used in the improved pest management practice compared with the traditional practice without these inputs. Pearson correlations for yield and economic return were negatively correlated for all pests and damage caused by pests. The results from these experiments can be used by farmers and their advisors to develop production packages for peanut production in Ghana.