Improved agronomy and plant nutrition are critical, yet often overlooked determinants of human health in Africa, influencing not only food security but also disease burden, income stability, and environmental resilience. In Ghana, this challenge is closely tied to socio-economic factors that influence farmers’ ability to adopt improved practices. This study shows the need for a dual approach: locally tailored promotion to suit situations where district-level differences are impacting relative adoption rates for ISFM, and unified, broad-based support programs for 4R Nutrient Stewardship which shows evidence of more consistent uptake by farmers. Together, these strategies can improve yields, strengthen soil health, and build climate resilience.