We conducted a quantitative study to identify the effectiveness of proton boron fusion therapy (PBFT). Four simulation scenarios were designed to investigate the escalation in total dose with the proton boron reaction using a Monte Carlo n-particle extended (MCNPX 2.6.0) simulation. The peak integrated dose was obtained for three different physical conditions (i.e., boron uptake region (BUR) thickness, BUR location, and boron concentration) with differing proton beam energy (60–90 MeV). We found that the peak integrated dose was increased by up to 96.62% compared to the pristine proton Bragg-peak. For the synergetic effect to take place with 60–70 MeV proton beam, the BUR had to be at least 0.3 cm thick while spanning the Bragg-peak. Similarly to the thickness, the BUR location needed to be within 0.3 cm from the Bragg-peak when the thickness was maintained at 0.9 cm. An effective proton boron reaction required the boron concentration to be equal to or greater than 14.4 mg/g. These results demonstrate the impact of various physical and beam conditions of the PBFT, which are critical environmental factors for the treatment planning. We envision that this study will advance our understanding of the PBFT, which can be an invaluable treatment method for maximizing the potential of proton therapy.