This study investigated the effect of cash flow optimality on investment returns in selected listed Manufacturing companies in Nigeria. The population consisted of listed 66 manufacturing companies on the Nigerian Stock Exchange. 25 of these manufacturing companies were purposively selected for a period of 10 years (2010-2019). The study employed data obtained from the published financial statement of the selected manufacturing companies. Panel data analysis was employed while diagnostic tests were carried out and an application of the Hausman test provided the criteria for choosing between Random Effect Models and Fixed Effect Models. Jarque-Bera Normality, Breusch, and Pagan Lagrangian multiplier tests were conducted to confirm the Hausman test results in order to decide between Random Effects and Pooled OLS. The study found that cash flow optimality had a positive statistically significant on return on assets, AdjR2 = 0.099; Wad-chi2 (4, 245) = 22.22; P-value = 0.000). Furthermore, the study revealed that cash flow optimality exhibited a positive statistical effect on Tobin’s Q, (AdjR2 = 0.130; F (4, 245) = 2.884; P-value = 0.025). Thus, the study recommended that since the essence of investment is the expected returns, managers of manufacturing companies should ensure that all strategic decisions are channeled towards this direction, and ensure efficient resources management and cash flow optimal management towards meeting investor returns expectations.