From economic and environmental perspectives, mineral fertilizers and organic resources should be targeted optimally within the cropping systems to ensure high productivity and high nutrient use efficiencies. This chapter reviews the status and determinants of the soil organic matter (SOM) status in maize-based farming systems and examines its critical role for maintaining the fertility and productivity of soils in Sub-Saharan Africa (SSA) and the implications for nutrient management decision support. It also reviews case study datasets of maize fertilizer trials to assess the extent to which SOM regulates maize productivity and fertilizer use efficiency and gain insights into the role of integrated soil fertility management practices in optimizing the agronomic performance of smallholder maize-based farming systems in SSA. On-farm nutrient omission trials conducted over six consecutive cropping seasons in western Kenya allow for the assessment of initial field soil organic carbon (SOC) status on spatial-temporal patterns in yield response to fertilizer N applications.