Biodiesel was produced from waste coffee grounds (WCGs) using solid catalysts manufactured from waste scallop shells through a one-step direct process (OSDP) comprising lipid extraction and simultaneous transesterification in a reactor. To facilitate the reuse of the solid catalysts, a cartridge containing the solid catalysts was devised, and the optimal conditions of the OSDP with the cartridge were investigated. Agitation speed was a critical factor for the operation of this novel process, and should be at least 200 rpm. The optimal total volume of the mixture consisting of methanol and n-hexane (9 mL/g-WCGs) was determined, along with the volume fraction of methanol (18.0%) and n-hexane (82.0%) using a statistical Mixture-Design technique. The optimum catalyst concentration (5.0 wt%), temperature (50°C), and reaction time (13 h) were determined through a Full Factorial Design, followed by a One-Factor-at-a-Time technique. Under these optimum conditions, 8.7% of biodiesel yield was obtained. The concentration of solid catalysts in the cartridge significantly influenced the reuse number of the cartridge. The cartridge containing 5.0 wt% of solid catalysts was reused only for the 2nd round of operation, while that containing 100 wt% of solid catalysts was successfully reused until the 12th round of operation, without a noticeable decrease in biodiesel yield.