<p>Inflammation is a complex biological response that varies significantly depending on the underlying disease or stress state, profoundly influencing the efficacy and safety of anti-inflammatory drugs. This review explores the multifaceted concept of drug-disease interactions in inflammatory conditions, highlighting how pathophysiological changes in autoimmune, metabolic, gastrointestinal, and infectious diseases modify pharmacokinetics and pharmacodynamics, thereby altering therapeutic responses and adverse effect profiles. We analyse a wide range of clinical studies and experimental models to elucidate the underlying mechanisms driving these interactions. The review further emphasizes personalized medicine approaches, including biomarker-guided therapies and pharmacogenomic insights, that enable tailored treatment strategies to improve patient outcomes. Strategies to optimize therapy in diverse disease states, such as drug repurposing and modulation in response to stress or comorbidities, are thoroughly examined. Additionally, emerging technologies and advanced experimental models are discussed to address current gaps and inform future research directions in conditional pharmacology. By synthesizing basic scientific knowledge with clinical practice, this comprehensive analysis aims to provide clinicians and researchers with critical insights necessary to enhance the safety and efficacy of anti-inflammatory treatments across a spectrum of inflammatory disorders.</p>