Abstract: Tin slag is a problematic residue with high economic value that is produced during the refining process of crude tin. Due to the highly refractory nature of these materials, the industrial extraction of the metals contained in the matrix depends on leaching with hydrofluoric acid, which poses problems in the handling and safety of materials. To minimize the effects related to the processing of these materials, a theoretical and experimental investigation was carried out to develop a process through thermal treatment, followed by aqueous or oxidative leaching to obtain a Pregnant Leach Solution (PLS) with the target metals. Here, an approach based on a thermodynamic simulation model is proposed to evaluate the optimal conditions for the maximum extraction of the Nb–Ta and Zr–Hf systems. The experimental results revealed that thermodynamic simulations allowed the identification of the ideal conditions for the formation of sulfates at 200°C, with a slag–H₂SO₄ ratio (g/mL) of 1:4 in a treatment time of 6 h, followed by two leaching routes. Aqueous leaching with a solid–liquid (S/L) ratio (g/mL) of 1:10 at 90°C for 2 h resulted in a recovery of 97% Nb, 61% Ta, 62% Zr, and 75% Hf. Meanwhile, oxidative leaching with a 0.5 M concentration, S/L ratio of 1:10 at 90°C for 2 h, resulted in a recovery of 81% Nb, 99% Ta, 98% Zr, and 99% Hf, confirming the efficiency of the process. This study highlights the importance of thermal treatment, thermodynamic modeling, water content, and the addition of oxidants in effective extraction, providing a pathway to optimize the recovery of economically valuable metals from tin slags.