“Controlled particle release and targeting” is a technique using particle release score map (PRSM) and transient particle release score map (TPRSM) via backtracking to determine optimal drug injection locations for achieving an enhanced target efficiency (TE). This paper investigates the possibility of targeting desired locations through an idealized but complex three-dimensional (3D) vascular tree geometry under realistic hemodynamic conditions by imposing a Poiseuille velocity profile and a Womersley velocity profile derived from cine phase contrast magnetic resonance imaging (MRI) data for steady and pulsatile simulations, respectively. The shear thinning non-Newtonian behavior of blood was accounted for by the Carreau–Yasuda model. One-way coupled Eulerian–Lagrangian particle tracking method was used to record individual drug particle trajectories. Particle size and density showed negligible influence on the particle fates. With the proposed optimal release scoring algorithm, multiple optimal release locations were determined under steady flow conditions, whereas there was one unique optimal release location under pulsatile flow conditions. The initial in silico results appear promising, showing on average 66% TE in the pulsatile simulations, warranting further studies to improve the mathematical model and experimental validation.