Post-harvest losses remain a significant challenge in Nigeria's agricultural sector, worsening food insecurity and economic instability. This study examines the impact of climatic stressors on PHL, identifying key climatic drivers and assessing their projected influence under future climate scenarios (SSP5-8.5). Using a combination of spatial analysis, Partial Least Squares Discriminant Analysis (PLS-DA), and Random Forest (RF) modelling, the study quantifies the relationship between temperature, precipitation, humidity, and post-harvest losses across Nigeria's six geopolitical regions. Findings reveal that temperature-related variables, such as maximum temperature (Txx), mean temperature (Tas), and heat days exceeding critical thresholds (HD35, HD40), significantly increase PHL, particularly in the northern regions. Conversely, precipitation (Pr) and relative humidity (Hurs) exhibit mixed effects, reducing losses in arid areas but exacerbating spoilage risks in humid zones. Economic implications are severe, with the North Central, North East, and North West regions accounting for over 80% of total financial losses. Additionally, the COVID-19 pandemic contributed to a 22.55% increase in PHL, highlighting vulnerabilities within Nigeria's food supply chain. Future projections under the SSP5-8.5 climate scenario indicate a continuous rise in losses, surpassing 250,000 tons by 2050. In response, climate-smart agriculture (CSA) is explored as a viable mitigation strategy. The adoption of heat- and drought-tolerant crop varieties, improved post-harvest storage technologies, integrated pest management, and climate-smart advisory services are proposed to enhance resilience against climate-induced losses. This study posits the necessity of integrating climatic variables in the quantification of PHL and also climate-responsive strategies into post-harvest loss mitigation frameworks in order to safeguard food security and agricultural sustainability in Nigeria.