Tomato seed oil biodiesel (TSOB) could be considered as a second-generation and clean-burning renewable substitute for petroleum diesel. It is about 72% by weight of tomato waste, which contains an average of 24% oil. This paper investigated the effects of four different diesel–TSOB blends on the combustion performance of an indirect injection (IDI) diesel engine. In-cylinder pressure (CP) and combustion parameters at five different engine loads and seven speeds were experimentally measured. Then for 2D computational fluid dynamics (CFD) simulation of the emissions and combustion processes, avl fire software was used and the results were evaluated with experimental data. The purpose of the study was to determine the combustion process and its effects on the performance and emissions of the engine. The outcomes for B10 at 100% load addressed that the peak CP of about 67 MPa was found at 1200 revolutions per minute (rpm) which occurred at 13 deg after top dead center (ATDC), while at 2200 rpm the peak CP was 69 MPa and occurred at 1 deg ATDC, and at 2400 rpm the peak CP was found to be about 66 MPa which occurred approximately at the top dead center (TDC). The simulated results found that the peak in-cylinder temperature of 1600 deg K corresponds to the 10% TSOB blend (B10) and the longest mixing-controlled period occurs for B10 at 27 deg crank angle (CA). The simulation also showed that B5 had the longest jet penetration of about 44 mm (at about 100 deg CA) in comparison to 43 mm for B20, 41 mm for B10, and 39.8 mm for B0 (pure diesel) which occurred at less than 100 deg CA. The longest jet penetration duration was found to be about 44 mm for B5 at about 100 deg CA. The results showed that B10 has the biggest accumulative heat release (approximately 1900 J) and the highest fuel energy efficiency. The 2D CFD simulation revealed that the unburnt equivalence ratio in the main combustion chamber is lesser than in the spherical combustion chamber.