Hyperpolarized [1-¹³C]pyruvate has emerged as a next-generation molecular probe for in vivo metabolic flux imaging in deep tissue. This molecular contrast agent is now under evaluation in over 50 clinical trials, according to clinicaltrials.gov. Hyperpolarized [1-¹³C]pyruvate is produced through dissolution dynamic nuclear polarization (d-DNP) for clinical research use. This remarkable hyperpolarization technique is regarded as expensive (>$2 M equipment cost) and slow (1 h production). One alternative hyperpolarization technique called Signal Amplification By Reversible Exchange (SABRE) in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) has recently garnered substantial attention for production of hyperpolarized [1-¹³C]pyruvate quickly (in 1 min) and inexpensively (<$20K equipment). It has been successfully demonstrated in vivo for metabolic imaging of cancer. This technique relies on the simultaneous chemical exchange of parahydrogen, acting as a source of nuclear spin order, and [1-¹³C]pyruvate on a Ir-IMes polarization transfer catalyst at ∼0.4 μm magnetic field. The SABRE catalyst forms two kinds of complexes with parahydrogen-derived hydrides, pyruvate, and dimethyl sulfoxide, acting as a critically important coligand; however, only the complex that binds pyruvate in an equatorial position can release hyperpolarized [1-¹³C]pyruvate into the solution to enable bulk HP [1-¹³C]pyruvate production for use in molecular imaging and other applications. Here, we investigate the interplay of pH and temperature with the SABRE-SHEATH hyperpolarization of [1-¹³C]pyruvate. Temperature and pH modulate this process in remarkable and complementary ways, greatly affecting pyruvate exchange and ¹³C relaxation dynamics. The overall process is optimal at pH (methanol) of 6.5−7.7 and a temperature of 6 °C: indeed, the catalyst-bound pyruvate exhibits high ¹³C polarization levels in excess of 25%. The ¹³C polarization results are additionally supported by ¹³C relaxation dynamics at a polarization field of 0.4