Nutrient depletion, organic matter loss, salinity, sodicity, and acidity are as a result of natural interactions that have tremendously resulted to decline in food and nutrient security and environmental quality. They are highly dynamic among different agro ecological regions. Most of the problems that cause these natural interactions are removal of crop residue, burning of crop residue, soil erosion and runoff, gaseous losses of nitrogen and leaching results to nutrient depletion; temperature, soil moisture and water saturation, soil texture, topography, vegetation and biomass production results to organic matter loss; low rainfall, high temperature, high evapotranspiration, inadequate drainage, deforestation, intensive cropping and over grazing result to salinity; sodic water, poor drainage, and deforestation result to sodicity; weathering and leaching, OM decomposition, acid rain, crop production and removal, application of acid forming fertilizer result to acidity. Nutrient depletion, organic matter loss, salinity, sodicity, and acidity could be managed through the combination of these practices; optimized timing and rate of fertility application, optimized use of agrochemical, use of organic fertilizer, use of cover crop, use of crop rotation and conservation tillage practice, mulching, efficient irrigation, use of tolerant crops, and liming. These practices, if effectively implemented will ameliorate the effects of nutrient depletion, organic matter loss, salinity, sodicity, and acidity thereby enhancing soil fertility for optimum crop production.