As several opinions and suggestions were made on the effect of the global economic meltdown on the Nigerian economy, however, few of these studies explored the impact of the crisis on the manufacturing sector of the economy. In this study, the effort is to provide empirical evidence of the impact on the sector. To achieve this, cross-sectional and time-series data were randomly collected from thirty-one (31) quoted firms across different sectors of the manufacturing sector and for a period of five years (2005-2009). A panel model analysis was employed as the estimating technique; it was considered as the most appropriate for the study. The objectives stated in the study were achieved, as the empirical findings revealed that the global economic meltdown had an impact on the Nigerian manufacturing sector. More so, the impact was negative on the sector and on its profitability all through the periods considered, as the impact was more severe in the year 2007. It was also revealed that profitability across the manufacturing firms in Nigeria is time-variant and cross sectionals variant. Finally, a set of policy recommendations were made as a result of the findings, in order to recognize the role of the manufacturing sector as the engine of growth, whose performance is crucial for economic dependency and transformation, these policies are to help in repositioning the sector from the bad state it was before and after the period of global economic crisis to an encouraging state: The sector need to have a strategic framework for industrial development that is domesticated, emphasis should be made on local sourcing of raw materials and technology so as to save guard the economy from the future severe impact of foreign economic shock, Government should ensure tight effective border control, power generation, transmission, and distribution should be improved, bailout funds and adequate credit should be made available. These and others, if carefully implemented, the manufacturing sector will be able to yield a positive result, possible as the driver of the economy by creating wealth, employment generation and economic prosperity.