Singlet-triplet gap (ΔES - T) and spin-orbit coupling (SOC) primarily govern intersystem crossing (ISC)-mediated photo- and electro-luminescence processes. Structural-twist in organic molecules is known to improve ISC efficiency. However, how and to what extent a twist affects the ΔES - T and SOC are not yet fully understood. In this work, the impact of molecular-twist on these energetics governing ISC is unveiled in a series of highly fluorescent prototype perylenediimides (PDIs) in dichloromethane implementing reliable quantum-chemical calculations. While S1 → T1 ISC remains suppressed with increasing twist, a relatively larger decrease in ΔES - T together with a modest increase in SOC results in enhanced S1 →T2 ISC. Significantly modulated ISC rates are predicted in a few experimentally relevant -CN- and -Br-substituted PDIs, where twist of varied extent arises naturally depending on substituent's chemical nature, numbers, and positions. This study uncovers the critical role of molecular-twist in tailoring ISC and thereby helps designing functional organic triplet-generating materials.