New approaches in isotope geochemistry require the development of novel methods for the isotopic analysis of crude oil, a typically complex and very hard to digest organic geological matrix. In this work, methods were developed for the determination of isotope ratios of Mg, Sr and Pb in crude oil by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). Two sample preparation methods, (i) microwave-assisted wet digestion within an ultra-high pressure digestion cavity (MAWD-PDC) and (ii) solubilization of inorganic solids as obtained after the ASTM D4807 test method, were evaluated. Using MAWD-PDC, up to 0.5 g of crude oil was efficiently digested using only 6 mL of 14.4 mol L⁻¹ HNO₃ (75 min, temperature up to 250 °C). MAWD-PDC was shown to be a suitable sample preparation method for subsequent determination of Mg, Sr and Pb isotope ratios. On the other hand, the ASTM method does not require sophisticated equipment. With this approach up to 10 g of oil can be dissolved in toluene and filtered through a nylon membrane and elements present as inorganic solids, such as Mg and Sr, are retained on the membrane and can be easily recovered in water. However, Pb was not recovered. Column chromatographic protocols for target element isolation were fine-tuned for each analyte to ensure quantitative yields. No statistical difference was observed between the results for Mg and Sr isotope ratios obtained using both sample preparation methods. A proof-of-concept study showed that the Mg–Sr–Pb isotopic composition of the Brazilian crude oils was within the range observed for seawater and the deposit bedrock, suggesting that the methods developed can be considered as promising tools to decipher the formation history of oil reservoirs.