This study examined the effects of industrialization and foreign direct investment (FDI) on poverty dynamics in Uganda under de-globalization conditions during the period 1990–2024. The study was motivated by persistent poverty despite continued efforts to promote industrial growth and attract FDI amid increasing global trade disruptions, supply chain fragmentation, and financial instability. Annual secondary data were obtained from the World Bank. A quantitative time-series research design was employed using Augmented Dickey-Fuller (ADF) unit root tests, Johansen cointegration, Vector Error Correction Model (VECM), Autoregressive Distributed Lag (ARDL), and Granger causality techniques. The findings revealed a strong long-run equilibrium relationship among poverty, industrial output, manufacturing, domestic investment, government expenditure, and FDI. Industrial output emerged as the most significant and consistent driver of poverty reduction in both the short and long run, while domestic investment and government expenditure also influenced poverty outcomes. However, FDI and manufacturing exhibited weaker and sometimes insignificant effects due to structural constraints, limited spillovers, and de-globalization-related disruptions. The study concludes that sustainable poverty reduction in Uganda depends largely on productive industrial expansion supported by efficient domestic investment and stable macroeconomic conditions. The study recommends strengthening industrial infrastructure, improving access to investment finance, enhancing local linkages between foreign investors and domestic firms, prioritizing pro-poor public expenditure, and promoting regional integration and digital trade systems to improve resilience under de-globalization.