“In Silico” research drives the world around us, as illustrated by the way our society handles climate change, controls the COVID-19 pandemic and governs economic growth. Unfortunately, the code embedded in the underlying data processing is mostly written by scientists lacking formal training in software engineering. The resulting code is vulnerable, suffering from what is known as threats to instrument validity. This position paper aims to understand and remedy threats to instrument validity in current “in silico” research. To achieve this goal, we specify a research agenda listing how recent software engineering achievements may improve “in silico” research (SE4Silico) and, conversely, how software engineering may strengthen its applicability (Silico4SE).