Obesity is considered one of the most crucial health problems of the century. Therefore, reducing obesity is critically important. Caffeine (CF) and chlorogenic acid (CLA), which are substantial components in green bean coffee which maximize thermogenesis in brown adipose tissue. In our study, we have prepared CF, CLA, and CF + CLA loaded-solid lipid nanoparticles (SLN) since the SLNs are cost-effective, tissue-localized, and highly stable. The central composite design model was preferred to select the optimized formulation. UHPLC was used for quantification related to the CF and CLA amounts. The high-pressure homogenization (HPH) method was used while SLN formulations were prepared in the presence of poloxamer® 407 (surfactant) and Compritol® 888 ATO (solid lipid). The nanoparticles were characterized, followed by the utilization of 3T3-F442A cell lines for the evaluation of the adipogenesis activity of the formulations. Then, rt-PCR and ELISA studies of adipogenic markers were conducted. After optimal formulations were selected with an average of 110.2 ± 0.1 nm, CF (1 mM) + CLA (0.5 mM)—loaded SLN formulation has been proven significantly effective by using PPAR-γ/C/EBP-a pathways. In a nutshell, our study has shown that CF + CLA loaded-SLN has been affected 45.8% times more than regular extracted coffee (p < 0.05) on the adipocyte cells. [Figure not available: see fulltext.].